Immune profile analysis of peripheral blood and tumors of lung cancer patients treated with immune checkpoint inhibitors.
Immune profile analysis of peripheral blood and tumors of lung cancer patients treated with immune checkpoint inhibitors.
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DOI：
10.21037/tlcr-22-421
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发表时间：
2022-11
影响因子：
4
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中科院分区：
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免疫检查点抑制剂（ICIs）已经成为肺癌药物治疗的核心，建立能够预测疗效和不良事件（ae）的生物标志物有待建立。我们前瞻性地分析了外周血单核细胞（PBMCs）与肺癌组织中免疫相关分子表达的关系，以及ICI单药治疗的效果。21例晚期非小细胞肺癌（NSCLC）患者接受ICI单药治疗。用流式细胞术分析注射ICI前后pbmc中免疫相关分子表达的变化。应用免疫组化（IHC）方法检测肿瘤细胞主要组织相容性复合体（MHC） I类、程序性细胞死亡配体1 （PD-L1）表达及肿瘤浸润免疫细胞在给药前的PD-L1、CD8、CD103表达。我们对21例患者进行了调查，其中腺癌11例，鳞状细胞癌10例。给予抗程序性细胞死亡蛋白-1 （PD-1）抗体18例和抗pd - l1抗体3例。临床反应分为完全缓解（CR） （n=1）、部分缓解（PR） （n=7）、病情稳定（SD） （n=10）和病情进展（PD） （n=3）。在PBMCs中表达的免疫相关分子中，给药后CD103+ CD39+ CD8+ T细胞的变化与临床反应密切相关。在无进展生存期（PFS）相关因素的单因素分析中，CD103+ CD39+ CD8+给药后细胞变化被确定为一个重要的预后因素，而CD103+ CD39+ CD8+给药后细胞变化和Brinkman指数是PFS相关因素的多因素分析中的独立预后因素。给药后CD103+ CD39+ CD8+细胞的变化可以预测ICIs的疗效。
Immune checkpoint inhibitors (ICIs) have become central to lung cancer drug therapy, and establishing biomarkers that can predict effects and adverse events (AEs) is awaited. We prospectively analyzed the association between the immune-related molecular expression in peripheral blood mononuclear cells (PBMCs) and lung cancer tissues, and the effects of ICI monotherapy. Twenty-one patients with advanced non-small cell lung cancer (NSCLC) who received ICI monotherapy were included. Changes in the expression of immune-related molecules in PBMCs before and after the administration of ICI were analyzed by flow cytometry. The major histocompatibility complex (MHC) class I and programmed cell death-ligand 1 (PD-L1) expression of cancer cells, and the PD-L1, CD8 and CD103 expression of tumor infiltrating immune cells in lung cancer tissue before the administration of ICI were confirmed by immunohistochemistry (IHC). Twenty-one patients were investigated, including 11 adenocarcinoma and 10 squamous cell carcinoma cases. Anti-programmed cell death protein-1 (PD-1) antibody (n=18) and anti-PD-L1 antibody (n=3) were administered. The clinical responses were graded as follows: complete response (CR) (n=1), partial response (PR) (n=7), stable disease (SD) (n=10) and progressive disease (PD) (n=3). Among immune-related molecules expressed in PBMCs, the CD103+ CD39+ CD8+ T cell change after administration closely correlated with the clinical response. In the univariate analyses of the factors associated with progression-free survival (PFS), CD103+ CD39+ CD8+ cell change after administration was identified as a significant prognostic factor, while the CD103+ CD39+ CD8+ cell change after administration and Brinkman index were independent prognostic factors in a multivariate analysis of the factors associated with PFS. The CD103+ CD39+ CD8+ cell change after administration may predict the efficacy of ICIs.