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.

Impact of ABCG2 polymorphisms on the clinical outcome of TKIs therapy in Chinese advanced non-small-cell lung cancer patients.

OBJECTIVE: The primary purpose of this study was to investigate the correlation between single nucleotide polymorphisms (SNPs) of ATP binding cassette superfamily G member 2 (ABCG2) and outcome of tyrosine kinase inhibitions (TKIs) therapy in Chinese advanced non-small-cell lung cancer (NSCLC) patients. The secondary objective was to identify biomarkers to evaluate the response to treatment and outcome of the targeted therapy. METHODS: SNP genotyping (34 G/A, 421 C/A, 1143 C/T and -15622 C/T) of ABCG2 gene in 100 patients was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The clinical characteristics of 100 patients were collected. A total of 70 patients were treated with TKIs (gefitinib, erlotinib and icotinib). The association between ABCG2 polymorphisms and clinical characteristics was evaluated. Kaplan-Meier survival curves were plotted for overall survival (OS) and analyzed with the log-rank test. RESULTS: The three polymorphisms of the ABCG2 34 G/A, 421 C/A and 1143 C/T occurred more frequently compared with -15622 C/T in Chinese advanced NSCLC patients. There was no association between ABCG2 polymorphisms and clinical characteristics (p > 0.05). The median OS of patients with GG genotype at position 34 of the ABCG2 gene was significantly shorter than those with GA or AA genotype (p < 0.05). No significant difference of OS was found in 421 C/A and 1143 C/T polymorphisms (p > 0.05). CONCLUSION: ABCG2 34 G/A may be a possible predictor of the clinical outcome of TKIs therapy in NSCLC patients.

Rechallenge with gefitinib following severe drug-induced hepatotoxicity in a patient with advanced non-small cell lung cancer: A case report and literature review.

Gefitinib has come to be the most widely used epidermal growth factor receptor-tyrosine kinase inhibitor in the treatment of advanced non-small cell lung cancer (NSCLC) in Asian patients. Common side effects include mild to moderate skin rash and diarrhea, however, drug-induced liver injury of varying severity is overlooked in long-term gefitinib administration and rarely reported. The current case report presents a female Chinese NSCLC patient who developed severe gefitinib-induced hepatotoxicity and was rechallenged with gefitinib following a 3-month break. The patient achieved partial clinical remission but developed drug-induced grade 4 hepatotoxicity following gefitinib administration for 14 months. As an alternative, 4 cycles of chemotherapy were administered to control tumor progression. Following restoration of the patient's liver function, gefitinib was rechallenged together with active hepatoprotective therapy. The patient presented good disease control and maintained normal liver function for >6 months. Thus, sequential chemotherapy and gefitinib rechallenge with hepatoprotective therapy may be a potential new treatment strategy for gefitinib-induced hepatotoxicity.