Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Department of Clinical Medicine, Shandong First Medical University, Jinan, Shandong, China.
Front Immunol. 2024 Oct 17;15:1464728. doi: 10.3389/fimmu.2024.1464728. eCollection 2024.
The shaping of the tumor immune microenvironment does not only rely on tumor-infiltrating lymphocytes but on the recruitment of lymphocytes in peripheral blood. Monitoring peripheral blood lymphocyte subsets level (PBLSL) can predict treatment response and prognosis with immune checkpoint inhibitors. This study investigated the heterogeneity of PBLSL in response to chemoradiotherapy (CRT) or combined with immunotherapy (CRIT) in advanced lung cancer patients.
77 patients with advanced lung cancer receiving CRT or CRIT were divided into treatment-responsive and non-responsive groups based on efficacy. The study analyzed short-term efficacy and progression-free survival (PFS) according to baseline PBLSL and explored the impact under different stratifications, including treatment modality, pathology type, and age.
In all patients, higher levels of B cells, higher CD4+/CD8+ T cell ratios, and lower CD8+ T cell levels were associated with better short-term outcomes (P = 0.0035, P = 0.044, P = 0.022). Subgroup analysis revealed that in the CRT group, higher B cell levels correlated with improved efficacy (P = 0.011) and superior PFS (P = 0.048, HR = 0.3886, 95% CI = 0.1696 to 0.8902). In the CRIT group, higher CD4+ T cell levels, lower CD8+ T cell levels, and higher CD4+/CD8+ T cell ratios were linked to better efficacy (P = 0.038, P = 0.047, P = 0.017). For adenocarcinoma patients, higher CD4+/CD8+ T cell ratios and lower CD8+ T cell levels predicted better efficacy (P = 0.0155, P = 0.0119). B cell levels were significant in squamous cell carcinoma (P = 0.0291), while no PBLSL was predictive for small cell lung cancer. Among patients under 65, higher B cell levels were linked to improved efficacy and prolonged PFS (P = 0.0036, P = 0.0332, HR = 0.4111, 95% CI = 0.1973 to 0.8563). For patients over 65, differences in CD4+ T cell levels and CD4+/CD8+ T cell ratios were significant (P = 0.0433, P = 0.0338).
PBLSL predicted efficacy and prognosis in various patient stratifications, suggesting PBLSL is a reliable predictor for CRT and CRIT in advanced lung cancer. Detecting different cellular subpopulations helps identify patients with significant treatment responses across different stratifications.
肿瘤免疫微环境的形成不仅依赖于肿瘤浸润淋巴细胞，还依赖于外周血中淋巴细胞的募集。监测外周血淋巴细胞亚群水平（PBLSL）可以预测免疫检查点抑制剂治疗的反应和预后。本研究探讨了晚期肺癌患者接受放化疗（CRT）或联合免疫治疗（CRIT）后 PBLSL 反应的异质性。
根据疗效将 77 例接受 CRT 或 CRIT 的晚期肺癌患者分为治疗反应组和非反应组。本研究根据基线 PBLSL 分析短期疗效和无进展生存期（PFS），并探讨了不同分层（治疗方式、病理类型和年龄）下的影响。
在所有患者中，较高的 B 细胞水平、较高的 CD4+/CD8+T 细胞比值和较低的 CD8+T 细胞水平与较好的短期疗效相关（P=0.0035、P=0.044、P=0.022）。亚组分析显示，在 CRT 组中，较高的 B 细胞水平与疗效改善相关（P=0.011）和 PFS 延长相关（P=0.048，HR=0.3886，95%CI=0.1696 至 0.8902）。在 CRIT 组中，较高的 CD4+T 细胞水平、较低的 CD8+T 细胞水平和较高的 CD4+/CD8+T 细胞比值与更好的疗效相关（P=0.038、P=0.047、P=0.017）。对于腺癌患者，较高的 CD4+/CD8+T 细胞比值和较低的 CD8+T 细胞水平预示着更好的疗效（P=0.0155、P=0.0119）。B 细胞水平在鳞状细胞癌中具有显著性（P=0.0291），而小细胞肺癌中无 PBLSL 具有预测性。在 65 岁以下患者中，较高的 B 细胞水平与疗效改善和 PFS 延长相关（P=0.0036、P=0.0332，HR=0.4111，95%CI=0.1973 至 0.8563）。对于 65 岁以上患者，CD4+T 细胞水平和 CD4+/CD8+T 细胞比值的差异具有显著性（P=0.0433、P=0.0338）。
PBLSL 在不同的患者分层中预测了疗效和预后，提示 PBLSL 是晚期肺癌 CRT 和 CRIT 的可靠预测指标。检测不同的细胞亚群有助于在不同的分层中识别具有显著治疗反应的患者。
