Association of lymphocyte subsets with efficacy and prognosis of immune checkpoint inhibitor therapy in advanced non-small cell lung carcinoma: a retrospective study

Abstract

Background: Immune checkpoint inhibitors (ICIs) have achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore biomarkers that could predict the survival outcomes and therapeutic efficacy in advanced NSCLC patients treated with immunotherapy. In this study, we aimed to assess the changes in peripheral blood lymphocyte subsets and their association with the therapeutic efficacy and clinical prognosis of advanced NSCLC patients treated with immunotherapy. Methods: A total of 276 patients with advanced NSCLC were enrolled. Peripheral blood lymphocyte subsets including CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells, Tregs and B cells were collected before any treatment, before immunotherapy or chemotherapy, and after 4 cycles of immunotherapy or chemotherapy. T-test was used to analyze the factors influencing lymphocyte subsets and their changes before and after therapy. Logistic regression was used to plot ROC curves and analyze the relationship between lymphocyte subsets and therapeutic efficacy. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subsets and progression-free survival (PFS). Results: Gender, distant metastasis, and EGFR mutation status are known to affect the proportion of peripheral blood lymphocyte subsets in patients with advanced NSCLC. The proportions of CD4+ T cells, CD8+ T cells, Tregs and B cells were found to decrease after chemotherapy as compared to the baseline. The proportion of CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells and Tregs were higher after immunotherapy than after chemotherapy. Compared to the baseline, the effective group showed significant increase in the proportions of CD4+ T cells, CD4+/CD8+ ratio, NK cells and Tregs, and the number of CD8+ T cells was significantly lower in the peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group did not show any significant differences in the above parameters. Baseline CD4+ T cells and NK cells were independent predictors of immunotherapy efficacy and PFS. Baseline Tregs were independent predictor of immunotherapy efficacy. Conclusion: Immune checkpoint inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy. The levels of the different lymphocyte subsets could serve as valuable predictive biomarkers of efficacy and clinical prognosis for NSCLC patients treated with immunotherapy.