Li Peng, Qin Peng, Fu Xiaomin, Zhang Guowei, Yan Xiangtao, Zhang Mina, Zhang Xiaojuan, Yang Jinpo, Wang Huijuan, Ma Zhiyong
Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Department of Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Ann Palliat Med. 2021 Mar;10(3):3039-3049. doi: 10.21037/apm-21-163.
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.
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.
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).
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.
本研究旨在评估外周血淋巴细胞亚群、T细胞程序性死亡受体1阳性（PD-1+）比例及其对肺癌无进展生存期（PFS）和影像学反应的影响。
2018年5月至2020年4月，招募河南省肿瘤医院34例诊断为晚期肺癌的患者。在接受免疫检查点抑制剂（ICI）治疗前后，通过流式细胞术评估外周血淋巴细胞亚群和T细胞的PD-1+比例。分别采用生存分析和Fisher精确检验评估这些参数与PFS及临床反应之间的相关性。
使用实体瘤疗效评价标准（RECIST）评估发现，多个淋巴细胞变量和生物标志物与PFS及肿瘤反应相关。在全部34例肺癌参与者以及28例非小细胞肺癌（NSCLC）参与者亚组中，ICI治疗前较高水平的自然杀伤（NK）细胞和较高的CD4+/CD8+细胞比值与更长的PFS相关。此外，在全部34例肺癌参与者中，CD4+T细胞与影像学反应显著相关。在28例NSCLC参与者中，治疗前CD4+T细胞水平较高、CD4+/CD8+细胞比值较高、NK细胞绝对数较高且调节性T细胞（Treg）水平较低者，肿瘤反应较好。在接受2周期ICI联合治疗后，在校正性别和中性粒细胞与淋巴细胞比值（NLR）后，CD4+T细胞和CD45+淋巴细胞的绝对数均与PFS具有统计学相关性[风险比（HR）分别为0.23，P = 0.015；HR = 0.30，P = 0.032]。CD45+、CD3+和CD4+T淋巴细胞的绝对数与ICI治疗的影像学反应相关（P = 0.038）。
我们的结果表明，治疗前NK细胞绝对数和CD4+/CD8+细胞比值可预测接受ICI联合治疗的肺癌患者更长的PFS和更好的影像学反应。此外，Treg以及淋巴细胞亚群中的其他参数也可能预测反应。
