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BACKGROUND@#Immune checkpoint inhibitor monotherapy is reported to have little effect in advanced non-small cell lung cancer (NSCLC) patients with driver oncogenes. However, recent studies have shown that some patients with driver genes are still benefit from combination immunotherapy after tyrosine kinase inhibitors (TKIs) drug resistance. The purpose of this study was to analyze the efficacy of posterior line immunotherapy in NSCLC patients with epidermal growth factor (EGFR) sensitive mutation, and to evaluate the value of immunotherapy in posterior line therapy in patients with advanced EGFR mutation.@*METHODS@#A total of 27 patients with EGFR mutation diagnosed in Beijing Chest Hospital, Capital Medical University from June 2018 to November 2020 were collected. After the progress of targeted therapy, they had received programmed cell death protein 1 (PD-1) checkpoint inhibitor combined with chemotherapy and anti-angiogenic drug therapy.@*RESULTS@#Of the 27 advanced NSCLC patients, 19 cases (70.4%) did not have T790M mutation. There were 8 cases (29.6%) with T790M point mutation. The total objective response rate (ORR) was 40.7%. Kaplan-Meier survival analysis showed that there was no statistically significant difference among different EGFR mutations (χ²=4.15, P=0.230). But progression-free survival (PFS) was significantly longer in patients without T790M mutation than in patients with T790M mutation (9.2 mon vs 3.3 mon, χ²=2.808, P=0.041), and the same trend was observed in patients with overall survival treated with the PD-1 inhibitor (12.2 mon vs 7.3 mon, χ²=3.22, P=0.062). ORR of patients without T790M was significantly better than that with T790M (52.63% vs 12.5%, P=0.045).@*CONCLUSIONS@#Patients with EGFR mutation can benefit from later-line combined immunotherapy. The patients with T790M mutation in the population of EGFR mutation had the worst effect of immunotherapy in the later line. Therefore, the follow-up treatment and whole-course management of these patients need to explore better treatment strategies to improve the benefit.
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BACKGROUND@#Lung cancer is the most common malignancy world-wide. There are a variety of immune infiltrating cells in tumor microenvironment, which is an important component of tumor immunity and has clinical significance for the prognosis of patients. CD45RO is a surface marker of memory T cells. The expression of CD45RO⁺ tumor infiltrating lymphocytes (TILs) is associated with the prognosis of many tumors. The purpose of this study was to evaluate the relationship between the density of CD45RO⁺ TILs in tumor and stromal area and the clinical characteristics of patients with non-small cell lung cancer (NSCLC) and its impact on the prognosis of patients. We aimed to explore the clinical value of CD45RO⁺ TILs and programmed cell death ligand 1 (PD-L1) as prognostic markers.@*METHODS@#Multiple fluorescent immunohistochemical staining was used to stain the tissue microarray chips of 167 patients with NSCLC, marking CD45RO, cytokeratin (CK) and PD-L1. Using artificial intelligence image recognition technology and tumor cell-specific CK staining, divide the tumor and stromal area in the tissue, evaluate the density of CD45RO⁺ TILs in the tumor and stromal area, and the expression level of PD-L1 in tumor cells. The non-parametric test was used to analyze the relationship between CD45RO⁺ TILs and the clinical characteristics of patients, and the Kaplan-Meier method and Cox risk ratio model were used to analyze the relationship between CD45RO⁺ TILs independently or in combination with PD-L1 and tumor prognosis.@*RESULTS@#The density of CD45RO⁺ TILs was significantly associated with patient age, smoking, tumor stage, and pathological type. Single-factor survival analysis showed that NSCLC (P=0.007) stromal region and lung adenocarcinoma (LUAD) (P<0.001) with CD45RO⁺ TILs high density had better OS. Multivariate survival analysis showed that the high density of CD45RO⁺ TILs in the stromal region of NSCLC (HR=0.559, 95%CI: 0.377-0.829, P=0.004) and lung adenocarcinoma (HR=0.352, 95%CI: 0.193-0.641, P=0.001) were independent prognostic factors for overall survival time (OS). Combined with PD-L1 score of tumor cells in tumor tissues and infiltration score of CD45RO⁺ TILs in all tumor tissues, the patients were divided into 4 groups: patients with PD-L1⁺/CD45RO⁺ had the longest disease-free survival (DFS) time, and patients with PD-L1⁺/CD45RO- had the shortest DFS time. Multivariate Cox regression analysis showed that PD-L1⁺/CD45RO- was an independent prognostic factor for DFS and had a higher risk of poor prognosis compared to the other three groups (HR=2.221, 95%CI: 1.258-3.919, P=0.006).@*CONCLUSIONS@#In tumor tissues, the density of CD45RO⁺ TILs, as well as the combination of CD45RO⁺ TILs and PD-L1 in tumor areas, significantly correlated with clinicopathological features and prognosis of NSCLC, which can be used as a new prognosis marker.
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BACKGROUND@#Immunotherapy represented by immune checkpoint inhibitors (ICIs) has been widely used in the treatment of lung cancer. There are controversies in clinical practice for patients with advanced non-small cell lung cancer (NSCLC) and high programmed cell death-ligand 1 (PD-L1) expression receiving ICIs monotherapy or combination chemotherapy.@*METHODS@#This study retrospectively analyzed the clinical data of 49 patients with advanced NSCLC and high PD-L1 expression. Immunohistochemistry was performed with 22C3 antibody, and the expression level of PD-L1 was evaluated according to tumor proportion score (TPS). Objective response rate (ORR) and progression free survival (PFS) were compared by groups of different clinical characteristics.@*RESULTS@#ORR of monotherapy and combination therapy group was 47.1% (8/17) and 43.8% (14/32), respectively, without statistical difference (P=0.825). The median PFS of monotherapy and combination therapy group was 8.0 months and 6.8 months, respectively, without statistical difference (P=0.502). Statistical analysis of predictors of immunotherapy for the patients showed first-line immunotherapy had better ORR than subsequent immunotherapy (12/19, 63.2% vs 10/30, 33.3%, P=0.041), however no difference in PFS. And there were no differences in ORR or PFS among groups of age, gender, smoking status, performance status (PS), pathological type, tumor size and tumor-node-metastasis (TNM) stage.@*CONCLUSIONS@#The therapeutic effect is similar between ICIs monotherapy and combination chemotherapy for patients with advanced NSCLC and high PD-L1 expression. ORR of first-line immunotherapy was better in patients with advanced NSCLC and high PD-L1 expression. The optimal treatment for this population remains further prospective clinical studies.
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Immunotherapy, in particular immune checkpoint inhibitors, has significantly improved the survival outcomes of advanced lung cancer patients and changed the treatment mode of lung cancer. In this article, we reviewed the mechanism of immunotherapy, the clinical trials that changed treatment guidelines, the important biomarkers, immune-related adverse events, and descripted the future of immunotherapy of advanced non-small cell lung cancer. .
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BACKGROUND: Human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hWJCs) via transplantation are able to survive in a dog model of intervertebral disc degeneration and to partially restore the height of the intervertebral disc. However, there is no study on whether hWJCs can repair nucleus pulposus cells after inflammatory injury as yet. OBJECTIVE: To observe the protective effect of hWJCs on interleukin-1β induced rat nucleus pulposus degeneration.METHODS: Nucleus pulposus cells at passage 3 from Sprague-Dawley rats were divided into three groups: (1) normal control group cultured in culture medium containing fetal bovine serum for 24 hours, and then cultured in complete medium for 24 hours; (2) intervention group with interleukin-1β intervention for 24 hours, followed by culture in the complete medium for 24 hours; (3) co-culture group with interleukin-1β intervention for 24 hours, followed by culture in the complete medium for non-direct co-culture with hWJCs for 24 hours. Annexin V-FITC/propidium iodide (PI) double staining and flow cytometry were used in succession to measure the apoptosis rate of nucleus pulposus cells in each group. The ADAMTS-4, MMPs-3 and TIMP-1 expression in nucleus pulposus cells was observed though RT-PCR. The activities of caspase-3, caspase-8 and caspase-9 were determined by caspase kit.RESULTS AND CONCLUSION: The apoptosis rates were ranked as follows: the intervention group > co-culture group > normal control group, and there were significant differences between groups (P < 0.05). Compared with the control group,the expression levels of ADAMTS-4 and MMPs-3 were significantly higher and the expression level of TIMP-1 was significantly lower in the intervention and co-culture groups (P < 0.05). Compared with the intervention group, the expression levels of ADAMTS-4 and MMPs-3 were significantly lower and the expression level of TIMP-1 was significantly higher in the co-culture group (P < 0.05). The expression activities of caspase-3, caspase-8 and caspase-9 were highest in the intervention group, followed by the co-culture group, and lowest in the normal control group, and there were significant differences between groups (P < 0.05). To conclude, hWJCs has obviously inhibitory effect on the apoptosis of degenerated nucleus pulposus cells induced by interleukin-1β.
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OBJECTIVE:To conduct the quality assessment of artificial Aquilaria sinensis by"cutting inducing technique", and provide reference for its scientific planting and harvest. METHODS:GC-MC and HPLC were adopted to detect the volatile in-gredients,characteristic spectrum,incense tetraol and alcohol-soluble extract contents in 3 batches of artificial A. sinensis(Num. 1, 2,3,respectively for 5,10,20 years)by"cutting inducing technique". RESULTS:The volatile ingredients of 3 batches of artifi-cial A. sinensis mainly consisted of aromatic compounds,sesquiterpene compounds,fatty acid compounds and chromone com-pounds. The characteristic spectrums of samples 2,3 were basically the same with the reference substance of A. sinensis. The in-cense tetraol contents of 3 batches of samples were 0.078%-0.254%,and alcohol-soluble extract contents were 12.4%-20.8%. The characteristic spectrum and the incense tetraol content of sample 1 were not conformed to the standards in Chinese Pharmacopoeia (2015 edition,part 1). CONCLUSIONS:Artificial A. sinensis by"cutting inducing technique"shows similar volatile ingredients to natural A. sinensis. The quality of artificial A. sinensis for more than 10 years is conformed to the standards in Chinese Pharmaco-poeia(2015 edition,part 1),which can be used as medicine,replacing the natural A. sinensis.
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OBJECTIVE:To conduct the quality assessment of artificial Aquilaria sinensis by"cutting inducing technique", and provide reference for its scientific planting and harvest. METHODS:GC-MC and HPLC were adopted to detect the volatile in-gredients,characteristic spectrum,incense tetraol and alcohol-soluble extract contents in 3 batches of artificial A. sinensis(Num. 1, 2,3,respectively for 5,10,20 years)by"cutting inducing technique". RESULTS:The volatile ingredients of 3 batches of artifi-cial A. sinensis mainly consisted of aromatic compounds,sesquiterpene compounds,fatty acid compounds and chromone com-pounds. The characteristic spectrums of samples 2,3 were basically the same with the reference substance of A. sinensis. The in-cense tetraol contents of 3 batches of samples were 0.078%-0.254%,and alcohol-soluble extract contents were 12.4%-20.8%. The characteristic spectrum and the incense tetraol content of sample 1 were not conformed to the standards in Chinese Pharmacopoeia (2015 edition,part 1). CONCLUSIONS:Artificial A. sinensis by"cutting inducing technique"shows similar volatile ingredients to natural A. sinensis. The quality of artificial A. sinensis for more than 10 years is conformed to the standards in Chinese Pharmaco-poeia(2015 edition,part 1),which can be used as medicine,replacing the natural A. sinensis.