Associations between peripheral blood lymphocyte subsets and clinical outcomes in patients with lung cancer treated with immune checkpoint inhibitor

Abstract

Background: This study aimed to estimate peripheral blood lymphocyte subsets and programmed death receptor-1 positive (PD-1+) proportions of T cells, and their impact on progression free survival (PFS) and radiological response in lung cancer. Methods: From May 2018 to April 2020, 34patients of the Henan Tumor Hospital who were diagnosed with advanced lung cancer were recruited to this study. Peripheral blood lymphocyte subsets and PD-1+ proportions of T cells were assessed by flow cytometry before and after treatment with immune checkpoint inhibitors (ICIs). The associations among these parameters, and PFS and clinical response were estimated by survival analysis and Fishers’ exact test, respectively. Results: Several lymphocyte variables and biomarkers were found to be correlated with PFS and tumor response, as assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). In all 34 lung cancer participants and a subgroup of 28 participants with non-small cell lung cancer (NSCLC), higher levels of natural killer (NK) cells and higher CD4+/CD8+ cell ratios before the ICIs treatment were associated with longer PFS. Moreover, CD4+ T cells were significantly correlated with radiological response in all 34 lung cancer participants. Of the 28 NSCLC participants, those with higher levels of CD4+ T cells, CD4+/CD8+ cell ratios, absolute numbers of NK cells, and lower levels of regulatory T cells (Tregs)before treatment had better tumor response. After 2 cycles of combined ICIs treatment, both the absolute numbers of CD4+ T cells and CD45+ lymphocytes were statistically associated with PFS after being adjusted for gender and neutrophil-lymphocyte ratio (NLR) [hazard ratio (HR) =0.23, P=0.015; HR=0.30, P=0.032, respectively]. The absolute numbers of CD45+, CD3+, and CD4+ T lymphocytes were associated with radiological response treated by ICIs (P=0.038). Conclusions: Our results suggested that the absolute number of NK cells and CD4+/CD8+ cells ratio before treatment could predict longer PFS and better radiological response in lung cancer patients treated with ICIs combination therapy. In addition, Tregs, as well as the other parameters in lymphocyte subsets, may also predict response.