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Immunotherapy,represented by immune checkpoint inhibitors(ICIs),has significantly changed the treat-ment strategy of non-small cell lung cancer(NSCLC)and has become an important therapy for all stages of NSCLC.However,there is an urgent need for further clarification regarding ICIs for elderly patients with advanced NSCLC.Treatment strategies for ICIs were guided by assessing survival data of elderly NSCLC patients included in clinical trials.We concluded that treatment regi-mens such as ICI monotherapy,dual immunotherapy,and ICIs combined with chemotherapy could be carried out in elderly NSCLC patients with a performance status(PS)score<2.Elderly NSCLC patients treated with ICIs could achieve similar benefits as younger patients and are generally well tolerated.However,as age increases(especially above 80 years),the efficacy decreased and the incidence of immune-related adverse events(irAEs)gradually increased.Therefore,ICIs should be carefully selected for advanced NSCLC patients at an advanced age.Compared to age,PS was a key factor causing patients to be excluded from ICIs and poorer survival outcomes.In conclusion,immunotherapy in elderly patients with advanced NSCLC is extremely challenging,and many issues still need further exploration in this field.
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Senescence is the major risk factor that promotes development of different stages of chronic liver diseases and is closely related to occurrence of hepatocellular carcinoma.Significant differences consist in clinicopathological features and tumor microenvironment between elderly and young patients with hepatocellular carcinoma.With rapid development of systemic therapy,immune checkpoint inhibitors combined with targeted therapy have greatly improved the prognosis of patients with advanced hepa-tocellular carcinoma.The selection of treatment decisions for elderly patients with hepatocellular carcinoma requires to consider u-nique age-related issues.Adequate communication and necessary evaluation should be carried out before making decisions.Elderly patients with hepatocellular carcinoma are speculated to benefit from combination immunotherapy based on age subgroup analysis of large clinical studies.However,data of effects and security obtained from clinical trials has certain limitations when being ap-plied in elderly populations of real world.The optimal therapeutic strategies for elderly patients with hepatocellular carcinoma still remain to be further explored in large-scale prospective clinical studies.
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Immune checkpoint inhibitors(ICIs)mainly including the CTL antigen 4(CTLA-4)and PD-1/PD-L1,which would offer a notable clinical benefit for non-small cell lung cancer(NSCLC)patients.By strengthening the antitumor immune re-sponse of the body,ICIs lead to immune-related adverse events(irAEs),including checkpoint inhibitor pneumitis(CIP).Although the clinical incidence of CIP is relatively low,some serious cases may prolong or terminate of immunotherapy,even life threateing.This article tries to summarize the clinical manifestations,pathological characteristics,biological mechanism,susceptible population,diagnosis and differential diagnosis,and integrated traditional Chinese and Western medicine treatment of CIP,in order to understand CIP more clearly.
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Immunocheckpoint inhibitors have been widely used in the treatment of various tumors. Although the incidence rate of immunocheckpoint inhibitor related myocarditis caused by them is low, the mortality is high. Cardiac magnetic resonance imaging is the gold standard for evaluating cardiac morphology and function, and it has important clinical application value in the grading diagnosis, risk stratification, adverse prognosis prediction, and treatment monitoring of immune checkpoint inhibitor associated myocarditis.
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Objective:To investigate the relationship between the expressions of checkpoint with forkhead-associated and ring finger(CHFR)and metastasis-associated protein 1(MACC1)and the sensitivity of patients with rectal cancer for neoadjuvant concurrent chemoradiotherapy(nCRT).Methods:The medical documents of 166 patients with rectal cancer admitted to First Hospital of Qinhuangdao from March 2017 to February 2022 were collected.All patients only received nCRT before surgery,and the radiotherapy adopted three-dimensional conformal intensity modulated radiotherapy,and chemotherapy adopted Capeox scheme.All patients successfully completed total mesorectal excision after 4-6 weeks of nCRT treatment.Immunohistochemical SP staining method was used to detect the protein expressions of CHFR and MACC1 in rectal cancer and its adjacent tissues.According to the tumor regressive grading(TRG)standard of the Joint Committee on Cancer Staging in the United States,75 patients who were grade 0-2 as TRG after nCRT were included in the nCRT insensitive group,and 91 patients who were grade 3-4 as TRG were included in the nCRT sensitive group.The expression levels of CHFR and MACC1 proteins in cancer tissues before and after treatment between the two groups were compared.And then,the relationship between clinically pathological characteristics of patients and nCRT sensitivity was analyzed,and the influencing factors of nCRT sensitivity were analyzed.The receiver operating characteristic(ROC)curves of them were drawn,and area under curve(AUC)values were calculated,and the predictive values of CHFR and MACC1 for the sensitivity of patients with rectal cancer to nCRT were further analyzed.Results:The CHFR positive expression rate in rectal cancer tissue was significantly lower than that in adjacent tissues of rectal cancer,and the MACC1 positive expression rate in rectal cancer tissue was significantly higher than that in adjacent tissues of rectal cancer(x2=81.373,87.150,P＜0.05),respectively.After 166 patients completed the nCRT treatment,there were 6 cases of TRG grade 0,8 cases of TRG grade 1,61 cases of TRG grade 2,59 cases of TRG grade 3 and 32 cases of TRG grade 4.The sensitivity rate of nCRT was 54.82%(91/166).The CHFR positive expression rate in the nCRT sensitive group was significantly higher than that in the nCRT insensitive group,and the MACC1 positive expression rate in the nCRT sensitive group was significantly lower than that in the nCRT insensitive group(x2=4.613,37.509,P＜0.05).The proportions of T4 stage and N+stage in the nCRT sensitive group were higher than those in the nCRT insensitive group,and the differences were statistically significant(x2=54.432,28.912,P＜0.05),respectively.The expressions of CHFR and MACC1 were respectively independent risk factor affected the sensitivity of patients with rectal cancer to nCRT[OR=2.456(95% CI:1.294-4.563),OR=3.281(95% CI:1.472-6.479),P＜0.05].The sensitivity and specificity of the combined detection of CHFR and MACC1 were respectively 65.89% and 69.46% in predicting the nCRT sensitivity for rectal cancer.The predictive value of the combined detection was higher than that of single CHFR detection and single MACC1 detection(AUC values of them were respectively 0.713,0.564,0.589,P＜0.05),respectively.Conclusion:CHFR and MACC1 are related to the sensitivity of patients with rectal cancer to nCRT,which means patients with high expression of CHFR and low expression of MACC1 are more sensitive to nCRT.Therefore,both of them may be indicators that predict the sensitivity of patients with rectal cancer to nCRT.
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Immune checkpoint inhibitors (ICIs) are currently used in the treatment of various tumors and play an important role in tumor treatment, resulting in many adverse reactions related to the immune system. Type 1 diabetes (T1DM) is a rare endocrine system complication, which is rarely reported at present. We report a case of T1DM after using ICIs to treat gastric cancer. The patient was a 34 year old male who developed diabetes ketoacidosis after 206 days of sintilimab monoclonal antibody use, with fasting blood glucose of 15.78 mmol/L and glycosylated hemoglobin of 8.6%. Islet related antibody: Glutamate decarboxylase antibody: 119.2 IU/mL; Insulin antibody:<2 IU/L. Fasting insulin: 0.21 mU/L; Fasting C-peptide: 0.12 μg/L. Through the analysis of patients' clinical data, it aims to improve clinicians' understanding of immune related type 1 diabetes and provide ideas for correct diagnosis and treatment.
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To summarize the nursing experience of a patient with gastric cancer who developed cytokine release syndrome after using immune checkpoint inhibitors.Key points of nursing care:development of nursing assessment decisions with a holistic view to guide safe nursing care;taking into account the contradiction between bleeding and thrombosis and providing good care for upper gastrointestinal bleeding;implementing a nursing strategy focusing on cleaning and anti-infection for IV oral mucositis;implementing risk management for severe pulmonary lesions;providing good hormone medication care and discharge follow-up management.The patient was successfully discharged on 52nd day with a 3-month follow-up in good condition.
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Objective:To investigate the efficacy of sintilimab combined with paclitaxel and docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:Prospective cohort study was performed. A total of 90 patients with advanced NSCLC receiving second-line treatment in Baotou Cancer Hospital from October 2019 to October 2022 were prospectively selected. All patients were divided into the study group (sintilimab combined with paclitaxel and docetaxel as second-line treatment, 45 cases) and the control group (paclitaxel or docetaxel alone, 45 cases) according to random number table method. The short-term efficacy, serum cytokine levels, quality of life and T-cell subsets of the two groups were compared. The survival of patients within 6 months was followed up. Kaplan-Meier method was used to analyze the overall survival (OS) of both groups, and log-rank test was used to make comparison among groups.Results:There were 25 males (55.56%) in the study group with the age of (63±5) years and 28 males (62.22%) in the control group with the age of (65±6) years. There were no statistically significant differences in the gender, age, Eastern Cooperative Oncology Group scores, the body mass (all P>0.05). The total effective rate was 88.89% (40/45) in the study group and 71.11% (32/45) in the control group, and the difference was statistically significant ( χ2 = 4.44, P = 0.035). The levels of serum vascular endothelial growth factor (VEGF) and carbohydrate antigen 125 (CA125) of both groups after treatment were lower than those before treatment (all P<0.001); the levels of VEGF and CA125 in the study group after treatment were lower than those in the control group [VEGF: (223±15) pg/ml vs. (289±15) pg/ml, t=20.82, P<0.001;CA125: (23±6) ng/ml vs. (75±4) ng/ml, t=51.28, P<0.001].Quality of life scale score, Karnofsky score of both groups after treatment were higher than those before treatment (all P<0.05); quality of life scale score and Karnofsky score in the study group after treatment were higher than those in the control group [quality of life scale score: (63±6) scores vs. (51±5) scores, t=10.29, P<0.001; Karnofsky score: (80.5±5.7) scores vs.(78.8±3.7) scores, t=1.70, P=0.041]. T-cell subsets indicators of both groups after treatment were higher than those before treatment (all P<0.001). T-cell subsets indicators in the study group after treatment were higher than those in the control group [CD3 + cell proportion: (68±5)% vs. (65±5)%, t=2.52, P = 0.014; CD4 + cell proportion:(42.5±1.7)% vs. (36.5±3.7)%, t=9.91, P<0.001;CD4 +/CD8 +: 1.78±0.54 vs. 1.46±0.27, t=3.56, P<0.001]. There was no significant difference in the incidence of adverse reactions between the two groups [11.11% (5/45) vs. 15.55% (7/45), χ2=0.39, P=0.534]. The follow-up time was 6 months. The OS in the study group was better than that in the control group ( χ2=3.86, P = 0.044). Conclusions:Sintilimab combined with taxoid chemotherapy drugs is effective in the second-line treatment of advanced NSCLC, and it improves immune function and shows a favorable safety.
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Objective:To investigate the clinical efficacy and safety of deep hyperthermia combined with sintilimab and nab-PC (albumin-bound paclitaxel + carboplatin) regimen in the treatment of advanced squamous non-small cell lung cancer (NSCLC) with driver gene negative and programmed death-1 receptor ligand 1 (PD-L1) expression positive.Methods:A prospective case-control study was performed. A total of 84 advanced squamous NSCLC patients with driver gene negative and PD-L1 expression positive in Hebei Seventh People's Hospital from January 2020 to December 2022 were collected, and all patients were divided into the observation group and the control group according to the random number table method, with 42 cases in each group. The control group was given the treatment of sintilimab combined with nab-PC regimen, and the observation group was given deep hyperthermia on the basis of the control group. After 4 consecutive cycles of treatment, the short-term efficacy of the two groups was compared. The levels of serum tumor markers [carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), cytokeratin fragment 19 (CYFR21-1)], and the positive expression rates of immunohistochemistry markers [p40, p63, and cytokeratin 5/6 (CK5/6)] before and after treatment were compared between two groups. Functional Assessment of Cancer Therapy-Lung cancer module (FACT-L) scores, the adverse reactions and the long-term survival of the two groups were compared.Results:There were 26 males and 16 females in the observation group, and the age was (59±11) years; there were 22 males and 15 females in the control group, and the age was (58±11) years. The objective remission rate and the disease control rate were 71.43% (30/42), 90.48% (38/42), respectively in the observation group, and 50.00% (21/42), 80.95% (34/42), respectively in the control group; the objective remission rate in the observation group was higher than that in the control group, and the difference was statistically significant ( χ2 = 4.04, P = 0.044); and there was no statistically significant difference in the disease control rate of both groups ( χ2 = 1.56, P = 0.212). The levels of serum CEA, SCCA and CYFRA21-1, and the positive expression rates of p40, p63, and CK5/6 in the two groups after treatment were lower than those before treatment (all P < 0.05); and the scores of physiological status, functional status, additional concern in FACT-L scores and the total score of the scale after treatment were higher than those before treatment (all P < 0.05). There were no statistically significant differences in the incidence of adverse reactions including thrombocytopenia, neutropenia, leukopenia, anemia, fever of the two groups (all P > 0.05). The median progression-free survival (PFS) time was 6.5 months (95% CI: 3.82-12.75), 5.1 months (95% CI: 3.14-12.26),respectively in the observation group and the control group, and the difference in the median PFS time was statistically significantly of both groups ( χ2 = 4.21, P = 0.040). The median overall survival (OS) time was 12.9 months (95% CI: 6.25-15.46), 9.7 months (95% CI: 4.74-13.02), respectively in the observation group and the control group, and the difference in the median OS time was statistically significantly of both groups ( χ2 = 4.43, P = 0.035). Conclusions:Deep hyperthermia combined with sintilimab and nab-PC regimen in the treatment of advanced squamous NSCLC with driver gene negative and PD-L1 expression positive can effectively reduce the serum tumor markers levels and positive expression rate of immunohistochemical markers, improve the quality of life of patients, and increase the short-term and long-term efficacy.
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@#The treatment of patients with advanced lung cancer has been revolutionized with the advent of immunotherapy. However, not all patients can benefit equally from immunotherapy. In recent years, the relationship between intestinal flora and the efficacy of immunotherapy has gradually attracted scholars' attention. During the treatment of immune checkpoint inhibitors, the use of antibiotics, proton pump inhibitors and other drugs will affect the patient's intestinal flora, thus affecting the efficacy of immune checkpoint inhibitors, leading to poor prognosis of patients. This review will discuss that antibiotics and proton pump inhibitors reduce the efficacy of immunotherapy by affecting the diversity of intestinal flora, in order to facilitate the rational use of related drugs in clinical practice and improve the patient's outcomes.
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ObjectiveTo investigate the safety and efficacy of tyrosine kinase inhibitors combined with immune checkpoint inhibitors in the treatment of patients with Child-Pugh class B unresectable hepatocellular carcinoma （uHCC）. MethodsA total of 96 patients with Child-Pugh class B uHCC who were admitted to Beijing Ditan Hospital， Capital Medical University， from December 31， 2020 to March 30， 2023 were enrolled as subjects， among whom 63 patients receiving lenvatinib combined with programmed death-1 （PD-1） inhibitor were enrolled as L group and 33 patients receiving sorafenib combined with PD-1inhibitor were enrolled as S group. The primary endpoint was objective response rate （ORR）， and secondary endpoints included time to progression （TTP）， overall survival （OS）， toxicity， drug withdrawal rate， and dose adjustment rate. The The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the Log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and its 95% confidence interval （CI） and perform the multivariate analysis of influencing factors for prognosis. ResultsAmong the 96 patients with uHCC， 55 （57.3%） had Child-Pugh class B （7 points） uHCC and 41 （42.7%） had Child-Pugh class B （8—9 points） uHCC. The L group had a significantly higher ORR than the S group （46.0% vs 15.2%， P=0.003）， and there were no significant differences between the L group and the S group in median TTP （6.6 months vs 3.5 months， P=0.48） or OS （13.8 months vs 13.2 months， P=0.95）. There was no significant difference in median TTP between the patients with Child-Pugh class B （7 points） uHCC and those with Child-Pugh class B （8—9 points） uHCC （6.6 months vs 4.8 months， P=0.35）， while there was a significant difference in OS between these two groups of patients （14.5 months vs 8.8 months， P=0.045）. The multivariate analysis showed that ORR was a protective factor for both TTP （HR=0.18， 95%CI： 0.09 — 0.36， P<0.001） and OS （HR=0.20， 95%CI： 0.09 — 0.43， P<0.001）. There were no significant differences between the L group and the S group in the overall incidence rate of adverse reactions （98.4% vs 97.0%） and the incidence rate of grade≥3 adverse reactions （68.3% vs 63.6%）， and there were also no significant differences between the two groups in dose adjustment rate （84.8% vs 70.2%） and drug withdrawal rate （56.1% vs 72.7%）. ConclusionCompared with the regimen of sorafenib combined with PD-1 inhibitor， the regimen of lenvatinib combined with PD-1 inhibitor can improve the ORR of patients with Child-Pugh class B uHCC， with similar prognosis and safety profile between the two groups.
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As an emerging cancer treatment modality, immunotherapy has shown promising efficacy in a variety of solid tumors, but it has failed to achieve a breakthrough in the treatment of prostate cancer.This review aims to provide an overview of the current applications of immunotherapy for prostate cancer, including immune-checkpoint inhibitors, cancer vaccines and chimeric antigen receptor T-cell (CAR-T), briefly describe the mechanisms of various immunotherapy modalities, summarize the results of clinical trials, and discuss the challenges and prospects.
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Immunotherapy has changed the treatment landscape of advanced non-small cell lung cancer (NSCLC), showing great potential in the treatment of untreated and relapsed or refractory (R/R) patients. However, numerous issues that need further exploration remain with the wide application of immunotherapy. They include the exploration of biomarkers for efficacy prediction, the optimization of immunotherapy modalities, immune-related adverse effects, and the management of special populations. This review summarizes the progress of the research on immunotherapy for advanced NSCLC and discusses its challenges and future directions.
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Objective To explore the significance of the combined strategy of oncolytic virus infection, immune effector cell supplement, and immune checkpoint blocking in the treatment of gastric cancer. Methods A tumor-bearing nude mouse model of gastric cancer was treated with recombinant oncolytic vaccinia virus carrying the CXCL9 gene of T lymphocyte chemokine and IL-7gene (VV-IL7-CXCL9) obtained in previous experiments. We established a triple-intervention group of recombinant oncolytic vaccinia virus intratumoral injection+cytotoxic T lymphocyte (CTL)+immune checkpoint blocker (PD-1 monoclonal antibody), a single-intervention group of three measures, a dual-intervention group, and a blank control group. After the intervention, tumor-growth curve method, tumor-inhibition rate method, and bioluminescence method were used to detect the tumor treatment effect. ELISA was used to detect CXCL9 and IL-7 molecule concentration in the serum and tissue homogenate of animals in each group. Results The therapeutic results of animal models showed that the tumor growth in the triple-intervention group of recombinant oncolytic poxvirus+CTL+immune checkpoint blocker (PD-1 monoclonal antibody) was significantly slower than those in the other intervention and the blank control group. Conclusion The combination of recombinant oncolytic poxvirus intratumoral injection+CTL+immune checkpoint blocker (PD-1 monoclonal antibody) exert a strong antitumor effect in intervention experiments on gastric-cancer animal models.
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ObjectiveTo investigate the efficacy and safety of cryoablation combined with Camrelizumab monoclonal antibody in the treatment of hepatocellular carcinoma （HCC）. MethodsA total of 103 HCC patients who were admitted to our hospital from June 2020 to June 2023 were enrolled and randomly divided into combined treatment group with 53 patients and control group with 50 patients. The patients in the control group received percutaneous argon-helium cryoablation， and those in the combined treatment group received percutaneous argon-helium cryoablation combined with Camrelizumab monoclonal antibody. The two groups were compared in terms of short-term response， changes in T lymphocyte subsets after treatment， changes in liver function and alpha-fetoprotein （AFP） after treatment， and progression-free survival and overall survival during follow-up. The t-test was used for comparison of normally distributed continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves， and the log-rank test was used for comparison of survival time between the two groups. ResultsThe combined treatment group had significantly higher overall response rate and disease control rate than the control group （χ2=4.156 and 4.348， P=0.042 and 0.037）. After treatment， the combined treatment group had significant increases in the percentages of CD3+ and CD4+ T lymphocytes and CD4+/CD8+ ratio （P<0.05） and a significant reduction in the percentage of CD8+ T lymphocytes （P<0.05）， while the control group had no significant changes in T lymphocyte subsets after treatment （P>0.05）， and compared with the control group after treatment， the combined treatment group had significantly higher percentages of CD3+ and CD4+ T lymphocytes and CD4+/CD8+ ratio （all P<0.05） and a significantly lower percentage of CD8+ T lymphocytes （P<0.05）. After treatment， both groups had significant reductions in the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and AFP （all P<0.05） and a significant increase in the level of albumin （Alb） （P>0.05）， and compared with the control group after treatment， the combined treatment group had significantly lower levels of ALT， AST， and AFP （all P<0.05） and a significantly higher level of Alb （P<0.05）. There were no significant differences in the incidence rates of grade Ⅲ—Ⅳ （moderate to severe） adverse reactions between the two groups （P>0.05）. Compared with the control group， the combined treatment group had significantly better median progression-free survival （21.32 months vs 15.31 months， χ2=4.689， P=0.030） and median overall survival （28.36 months vs 20.75 months， χ2=5.030， P=0.025）. ConclusionArgon-helium cryoablation combined with Camrelizumab monoclonal antibody can effectively improve short-term response， enhance immune function， and prolong survival time， with a favorable safety profile.
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T cell dysfunction is a common feature in patients with acute myeloid leukemia (AML). The up-regulation of immune checkpoint (IC) proteins resulting in T cell exhaustion is a key reason for T cell dysfunction. Immunotherapy with IC inhibitors exerts a remarkable effect on AML. However, due to the heterogeneity of T cell exhaustion and other factors that impair T cell function in patients with AML, the optimization of targeted T cell immunotherapy strategy for AML might be based on the multidimensional investigation of immune deficiency with different T cell subtypes.
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Monopolar spindle 1, also known as threonine and tyrosine kinase (TTK), is a key component of spindle assembly checkpoint (SAC). It is considered to be a monitoring mechanism to ensure mitotic fidelity and genomic stability. TTK is overexpressed in a variety of malignant tumors, and patients with low expression of TTK tend to have a longer survival time, suggesting that it may be used as a biomarker for diagnosis and prognosis. Abnormal expression of TTK often impairs the function of SAC, resulting in irregular mitosis, increased aneuploidy and mitotic disaster, thus promoting the occurrence of tumors. Current studies have shown that TTK inhibitors can inhibit the proliferation of tumor cells and increase the sensitivity of tumor cells to therapy in combination with chemotherapy or radiotherapy to achieve sensitization and attenuated effects. This article will review the research and application of TTK and its inhibitors in malignant tumors.
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Objective:To investigate the efficacy of immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma (ESCC) in the real world.Methods:The clinical data of 65 patients with stage Ⅲ-ⅣA ESCC treated by radical radiotherapy and chemotherapy from January 1, 2018 to December 31, 2022 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed. According to whether to undergo immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy, the patients were divided into a control group ( n=29) and an immune maintenance therapy group ( n=36) . The objective response rate (ORR) , progression-free survival (PFS) , and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to conduct both univariate and multivariate analyses. Results:The ORR was 34.5% (10/29) in the control group and 61.1% (22/36) in the immune maintenance therapy group, with a statistically significant difference ( χ2=4.56, P=0.032) . The median PFS of control group and immune maintenance therapy group were 7.2 and 17.9 months, respectively, with a statistically significant difference ( χ2=7.86, P=0.005) . The median OS was 14.1 and 27.8 months, respectively, with a statistically significant difference ( χ2=5.40, P=0.020) . Univariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.28, P<0.001) and immune maintenance therapy ( HR=0.38, 95% CI: 0.17-0.88, P=0.024) were the influential factors of OS in ESCC patients treaded by radical chemoradiotherapy in stage Ⅲ-ⅣA. Multivariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.29, P<0.001) and immune maintenance therapy ( HR=0.40, 95% CI: 0.17-0.92, P=0.032) were the independent influencing factors for OS in ESCC patients treaded by radical chemoracial therapy in stage Ⅲ-ⅣA. The incidence of adverse reactions was 22.22% (8/36) in the immune maintenance therapy group and 10.34% (3/29) in the control group, with no statistically significant difference ( χ2=1.61, P=0.204) . All the adverse reactions were grade 1-2, and the symptoms were relieved after symptomatic treatment. Conclusion:Maintenance therapy with immune checkpoint inhibitors after radical chemoradiotherapy of stage Ⅲ-ⅣA ESCC can significantly improve the prognosis of patients with good safety.
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Objective:To explore the predictive value of early serum tumor markers (STM) , neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) combination score on the efficacy of gastric cancer immunotherapy.Methods:A total of 76 patients with gastric cancer who received immunotherapy at Second Affiliated Hospital of Shandong First Medical University from January 1, 2020 to June 30, 2022 were selected. Patients' leading STM, NLR, PLR were collected. Optimal cut-off value of NLR and PLR were determined by the receiver operating characteristic (ROC) curve. The clinical efficacy and prognosis of different leading STM, NLR, PLR and combined scores in gastric cancer patients received immunotherapy were analyzed. ROC curve was used to evaluate the predictive efficiency of each index and the combined score. Cox regression model was used to analyze the factors affecting patients' survival.Results:The best truncation value for NLR was 2.75, and the best truncation value for PLR was 175.9. All patients completed at least 2 cycles of immunotherapy, the objective response rate (ORR) was 23.7% (18/76) , and the disease control rate (DCR) was 88.2% (67/76) . There were no significant differences in ORR [ (20.9% (9/43) vs. 27.3% (9/33) ], DCR [83.7% (36/43) vs. 93.9% (31/33) ] between the high NLR group ( n=43) and low NLR group ( n=33) ( χ2=0.42, P=0.519; χ2=1.02, P=0.313) . There were no significant differences in ORR [27.3% (12/44) vs. 18.8% (6/32) ], DCR [81.8% (36/44) vs. 96.9% (31/32) ] between the high PLR group ( n=44) and low PLR group ( n=32) ( χ2=0.75, P=0.388; χ2=2.71, P=0.555) . The ORR for the high combined score group ( n=39) and low combined score group ( n=37) was 17.9% (7/39) and 29.7% (11/37) , respectively, with no statistically significant difference ( χ2=1.46, P=0.230) ; the DCR was 79.5% (31/39) and 97.3% (36/37) , respectively, with a statistically significant difference ( χ2=4.19, P=0.041) . The median progression free survival (PFS) and overall survival (OS) of 76 patients were 8.0 and 12.0 months. The median PFS in the high NLR group and low NLR group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=7.95, P=0.005) ; the median OS was 12.0 and 14.0 months, respectively, with no statistically significant difference ( χ2=1.04, P=0.307) . The median PFS in the high PLR group and low PLR group was 8.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=3.90, P=0.048) ; the median OS was 13.0 and 13.0 months, respectively, with no significant difference ( χ2=0.02, P=0.896) . The median PFS in the high combined score group and low combined score group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=13.52, P<0.001) ; the median OS was 12.0 and 14.0 months, respectively, with a statistically significant difference ( χ2=5.02, P=0.025) . ROC curve analysis showed that the area under curve (AUC) of leading STM, NLR, PLR and combined score to predict the efficacy of gastric cancer immunotherapy was 0.662, 0.697, 0.601 and 0.773. Univariate analysis showed that, surgery ( HR=0.59, 95% CI: 0.36-0.95, P=0.031) , leading STM ( HR=0.57, 95% CI: 0.34-0.93, P=0.026) , NLR ( HR=0.54, 95% CI: 0.34-0.87, P=0.011) , combined score ( HR=0.42, 95% CI: 0.26-0.68, P<0.001) were all influencing factors for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.30, 95% CI: 0.12-0.75, P=0.011) , leading STM ( HR=0.28, 95% CI: 0.15-0.50, P<0.001) , combined score ( HR=0.55, 95% CI: 0.31-0.96, P=0.036) were all influencing factors for OS in gastric cancer patients received immunotherapy. Multivariate analysis showed that, leading STM ( HR=0.56, 95% CI: 0.33-0.98, P=0.041) was an independent influencing factor for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.29, 95% CI: 0.11-0.76, P=0.012) , leading STM ( HR=0.32, 95% CI: 0.17-0.58, P<0.001) , combined score ( HR=0.46, 95% CI: 0.25-0.82, P=0.009) were all independent influencing factors for OS in gastric cancer patients received immunotherapy. Conclusion:The combined score of leading STM, NLR and PLR is an independent factor influencing OS in patients receiving immunotherapy for gastric cancer, and can predict the efficacy of immunotherapy for gastric cancer.
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Objective To investigate the efficacy of histone deacetylase(HDAC)inhibitor chidamide combined with the PD-1 inhibitor on CD8+ T cells anti-cancer function in OVA-expressing MC38(MC38-OVA)colorectal-bearing mice.Methods Animal experiments:C57BL/6 tumor models were constructed by subcutaneously injecting MC38-OVA colorectal cancer cells into the back of mice.We randomized mice into control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group(20 each group).We monitored the tumor growth and animal survival rate of each group;we employed a flow-based method to detect the number and ratio of tumor-infiltrating CD8+ T cells,CD8+IFN-γ+ T cells,OVA antigen-specific CD8+ T cells,and the expression changes of regulatory T cells(Treg),myeloid-derived suppressor cells(MDSC),and tumor-associated macrophages(TAM).Cell experiments:We used a flow-based method to detect the apoptosis of CD8+ T cells and MC38-OVA tumor cells after 0,10,25,50,100,or 200 nmol/L chidamide treatment.The proliferation of CD8+ T cells and MC38-OVA tumor cells treated with 0 and 100 nmol/L chidamide was detected by Ki-67 antibody labeling and cell counting.To evaluate CD8+ T cell killing ability,we treated CD8+ T cells with various conditions(control group,chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group)followed by co-culture with MC38-OVA tumor cells,using the flow-based method.In the condition that CD8+ T cells treated with 0 and 100 nmol/L chidamide co-cultured with the same number of MC38-OVA tumor cells,the expression of CD107a was detected by flow cytometry.Results Compared with control group,the tumor growth was inhibited(P<0.05)while the survival rate was improved(P<0.01)in chidamide+anti-PD-1 group.The number of tumor-infiltrating CD8+ T cells was significantly higher in chidamide group,anti-PD-1 group and chidamide+anti-PD-1 group than that in control group(P<0.05).Nonetheless,the ratio and levels of CD8+IFN-γ+ and OVA antigen-specific CD8+ T cells were significantly higher in chidamide+anti-PD-1 group than those in other groups(P<0.05).The in vitro experiment results showed that chidamide could enhance the killing ability of CD8+ T cells and the expression of CD107a.Conclusion Chidamide combined with PD-1 inhibitor significantly enhanced the number and function of tumor-infiltrating CD8+ T cells and increased antigen-specific CD8+ T cells,which will provide a theoretical and experimental basis for the combination of chidamide in clinical solid tumor immunotherapy.