Circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio predict response and outcome to immunotherapy in advanced gastric cancer patients.

BACKGROUND: Limited benefit population of immunotherapy makes it urgent to select effective biomarkers for screening appropriate treatment population. Herein, we have investigated the predictive values of circulating CD8+ T cells and CD8+T/CD4+T cell ratio in advanced gastric cancer patients receiving immunotherapy. METHODS: A retrospective cohort analysis of 187 advanced gastric cancer patients receiving sintilimab combined with oxaliplatin and capecitabine therapy in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University between December 2019 and February 2023 was conducted. The corresponding clinical outcomes of the variables were analyzed by receiver operating characteristic (ROC) curve, chi-square test, Kaplan-Meier methods and Cox proportional hazards regression models. RESULTS: The optimal cutoff values for percentages of CD8+ T cells, naive CD8+ T cells (CD8+ Tn) and memory CD8+ T cells (CD8+ Tm) expressing programmed cell death -1(PD-1) as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were 21.0, 21.5, 64.3 and 0.669, respectively. It was found that the mean percentages of CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were significantly higher in responder (R) than non-responder (NonR) advanced gastric cancer patients associated with a longer progression free survival (PFS) and overall survival (OS). We also observed this correlation in programmed cell death-ligand 1(PD-L1) combined positive score (CPS) ≥ 5 subgroups. Univariate and multivariate Cox regression analyses demonstrated that lower CD8+ T and CD8+ Tm expressing PD-1 as well as PD-1+CD8+T/PD-1+CD4+T cell ratio were independent risk factors in advanced gastric cancer patients receiving immunotherapy plus chemotherapy. CONCLUSION: The circulating memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio revealed high predictive values for response and prolonged survival outcomes in advanced gastric cancer patients receiving immunotherapy. Memory PD-1+CD8+ T cells and PD-1+CD8+T/PD-1+CD4+T cell ratio might be effective for screening benefit population of immunotherapy in advanced gastric cancer patients based on this preliminary evidence.

Predictive value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma treated with camrelizumab.

Nutritional indicators have been implicated in the survival outcomes of various malignant tumors. However, there are few studies on the association between nutritional indicators and immunotherapy for esophageal cancer. The present study aimed to explore the value of nutritional indicators with regard to the survival outcomes in patients with metastatic esophageal squamous cell carcinoma (ESCC) treated with camrelizumab. A retrospective cohort analysis of 158 metastatic ESCC patients treated with camrelizumab in The Affiliated Xinghua People's Hospital, Medical School of Yangzhou University (Xinghua, China) between September 2019 and July 2022 was conducted. A receiver operating characteristic curve was used to determine the optimal cut-off values of prognostic nutritional index (PNI) and albumin (ALB). The cut-off value for body mass index (BMI) was set at the normal lower limit (18.5 kg/m2). Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and the differences in PFS or OS between groups were compared using the log-rank test. The prognostic value of each variable was analyzed based on the univariate and multivariate Cox proportional hazards regression models. The optimal cutoff values of PNI, ALB and BMI were 41.35, 36.8 g/l and 18.5 kg/m2, respectively. Lower PNI, ALB and BMI were closely associated with shorter PFS [hazard ratio (HR) for PNI, 3.599; P<0.001; HR for ALB, 4.148; P<0.001; HR for BMI, 5.623; P<0.001) and OS (HR for PNI, 7.605; P<0.001; HR for ALB, 7.852; P<0.001; HR for BMI, 7.915; P<0.001) times. Univariate and multivariate Cox regression analyses indicated that lower PNI, ALB and BMI were independent risk factors of PFS and OS in patients with metastatic ESCC receiving camrelizumab treatment. In conclusion, PNI, ALB and BMI are promising predictive indicators to assess the survival outcomes in patients with metastatic ESCC treated with camrelizumab. Moreover, PNI, ALB and BMI may have prognostic significance in these patients.

The Predictive Value of Systemic Inflammatory Factors in Advanced, Metastatic Esophageal Squamous Cell Carcinoma Patients Treated with Camrelizumab.

Objective: Systemic inflammatory factors are independent risk factors in the formation and progression of various solid tumors. However, whether systemic inflammatory factors are associated with effect and prognosis of esophageal squamous cell carcinoma patients treated with immunotherapy remains unknown. The aim of this study is to assess the value of systemic inflammatory factors in the efficacy of camrelizumab for patients with advanced, metastatic esophageal squamous cell carcinoma. Methods: We conducted a retrospective analysis of 90 patients with advanced, metastatic esophageal squamous cell carcinoma who received treatment with camrelizumab in Xinghua People's Hospital between August 2019 and October 2021. The optimal cut-off values of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) for predicting efficacy and prognosis were identified based on the receiver operating characteristic (ROC) curve. Progression free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method, and differences in PFS or OS between groups were compared by the Log rank test. Univariate and multivariate Cox proportional hazards regression models were performed to analyze prognostic values of each variable. Results: The optimal cutoff values of PLR, NLR and SII predicted survival outcomes were 157.7, 3.84 and 750.8, respectively. Higher PLR, NLR and SII were associated with shorter PFS (HR for PLR = 2.899, P = 0.001; HR for NLR = 3.629, P < 0.001; HR for SII = 10.251, P < 0.001) and OS (HR for PLR = 4.583, P < 0.001; HR for NLR = 3.921, P < 0.001; HR for SII = 38.606, P < 0.001). Multivariate Cox regression analysis revealed that high PLR, NLR and SII were independent risk factors of PFS and OS in the advanced, metastatic esophageal squamous cell carcinoma patients receiving camrelizumab. Conclusion: PLR, NLR and SII are potentially effective prognostic predictors in advanced, metastatic esophageal squamous cell carcinoma patients treated with camrelizumab.

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

IMPORTANCE: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. OBJECTIVE: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. INTERVENTIONS: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. RESULTS: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02813967.

The Long Noncoding RNA LOXL1-AS1 Promotes the Proliferation, Migration, and Invasion in Hepatocellular Carcinoma.

OBJECTIVE: To investigate the expression of long noncoding RNA lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) in hepatocellular carcinoma tissues and its effect on cell proliferation, migration, and invasion. METHODS: Quantitative real-time PCR was used to analyze the expression of LOXL1-AS1 RNA in tumor tissues, adjacent normal tissues, and cell lines. MTT assay, colony formation assay, flow cytometry analysis, transwell assays, and lentivirus-mediated RNA interference (RNAi) technology were used to evaluate cell proliferation and migration. RESULTS: In the present study, we observed that the expression level of LOXL1-AS1 in hepatocellular carcinoma tissue was significantly higher than that in adjacent nontumor tissues, and its expression in three hepatic carcinoma cell lines was obviously higher than that in a normal cell line. In addition, in the Hep-G2 cell line, LOXL1-AS1 downregulation significantly inhibited cell proliferation in the light of the MTT and colony formation assays in vitro, which was consistent with animal experiment in vivo. What is more, cell migration was also inhibited in vitro in Matrigel Transwell Assay by LOXL1-AS1 knockdown, which might be partly attributed to the reduction of MMP-2 and MMP-9 protein expressions. Finally, cell cycle analysis revealed that knockdown of LOXL1-AS1 induced significantly a G0/G1 phase cell cycle arrest, which might be partly attributed to the downregulation of Cdc2, Cdc25A, and cyclin B1 protein expression. CONCLUSION: In conclusion, we demonstrated that reduced LOXL1-AS1 expression could inhibit hepatocellular carcinoma cell proliferation, migration, and invasion. The application of RNAi targeting LOXL1-AS1 might be a potential treatment strategy in advanced cases.

Potential predictors of sensitivity to pemetrexed as first-line chemotherapy for patients with advanced non-squamous NSCLCs.

BACKGROUND: Pemetrexed (PEM) is effective in first-line treatment for patients with non-squamous non-small cell lung cancer (NSCLC). However there are currently no definitive determinants to certify which patients could benefit from PEM. To improve the efficacy of PEM combined with platinum as first-line therapy for advanced non-squamous NSCLC, we conducted this retrospective study to detect potential determinants of this regimen. METHODS: We recruited 109 patients with advanced non-squamous NSCLC who received PEM with a platinum as first-line therapy from June 2006 to February 2013 in Jiangsu Cancer Hospital. Multiple variables (age, sex, smoking, degree of cell differentiation, hemoglobin, platinum drugs combined, positions of metastasis) were selected. Logistic regression analysis was used to analyse relationships between these variables and tumor response. RESULT: In univariate analysis, we found that age and platinum significantly influenced the results of PEM therapy (P<0.05). In multivariable analysis, no factors were independently significant. CONCLUSION: Our analysis did not suggest that the age, sex, metastasis of liver or other organs, hemoglobin, smoking history and pathological differentiation are associated with the response of PEM. We should conduct further analyses with larger sample size to reconfirm this issue.