Chen Ling, Tan Hourui, Geng Ruixuan, Li Yifan, Wang Yingyi, Li Taisheng
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Thorac Cancer. 2025 Jan;16(1):e15493. doi: 10.1111/1759-7714.15493. Epub 2024 Nov 24.
Our study aimed to comprehensively describe the features of peripheral blood multiple immune cell phenotypes in solid tumor patients during pretreatment and after immunotherapy, providing a more convenient approach for studying the prognosis of immunotherapy in different solid tumor patients.
We prospectively recruited patients with advanced solid tumors from Peking Union Medical College Hospital (PUMCH) between February 2023 and April 2024. Using multicolor flow cytometry, our study comprehensively observed and described the signatures of peripheral blood lymphocyte subsets including activation, proliferation, function, naïve memory, and T cell exhaustion immune cell subsets in this population of pretreatment and after immunotherapy.
Our study enrolled 59 advanced solid tumor patients with immunotherapy and 59 healthy controls were matched by age and gender. The results demonstrated a marked upregulation in the expression of lymphocyte activation markers CD38 and HLA-DR, as well as exhaustion and proliferation markers PD-1 and Ki67, in solid tumor patients compared to healthy controls. After immune checkpoint blockade (ICB) treatment, mainly the expression of Ki67CD4+T and HLA-DRCD38CD4+T, was significantly upregulated compared to pretreatment levels (p = 0.017, p = 0.019, respectively). We further found that gynecological tumors with better prognoses had higher baseline activation levels of CD4+ T cells compared to other solid tumors with poorer prognoses.
Our study elucidated the characteristics of different lymphocyte subsets in the peripheral blood of solid tumor patients. Further research revealed changes in the phenotypes of different lymphocyte subsets after ICIs treatment, with the activated phenotype of CD4+ T cells playing a crucial role in the antitumor effect. This lays the groundwork for further exploration of prognostic biomarkers and predictive models for cancer patients with immunotherapy.
本研究旨在全面描述实体瘤患者在预处理期间及免疫治疗后的外周血多种免疫细胞表型特征，为研究不同实体瘤患者免疫治疗的预后提供更便捷的方法。
我们于2023年2月至2024年4月前瞻性招募了北京协和医院（PUMCH）的晚期实体瘤患者。本研究采用多色流式细胞术，全面观察并描述了该人群预处理及免疫治疗后外周血淋巴细胞亚群的特征，包括激活、增殖、功能、初始记忆以及T细胞耗竭免疫细胞亚群。
本研究纳入了59例接受免疫治疗的晚期实体瘤患者，并匹配了59名年龄和性别相匹配的健康对照。结果表明，与健康对照相比，实体瘤患者淋巴细胞激活标志物CD38和HLA-DR以及耗竭和增殖标志物PD-1和Ki67的表达显著上调。免疫检查点阻断（ICB）治疗后，主要是Ki67CD4+T和HLA-DRCD38CD4+T的表达与预处理水平相比显著上调（分别为p = 0.017，p = 0.019）。我们进一步发现，与其他预后较差的实体瘤相比，预后较好的妇科肿瘤CD4+T细胞的基线激活水平更高。
本研究阐明了实体瘤患者外周血中不同淋巴细胞亚群的特征。进一步研究揭示了免疫检查点抑制剂（ICIs）治疗后不同淋巴细胞亚群表型的变化，其中CD4+T细胞的激活表型在抗肿瘤作用中起关键作用。这为进一步探索癌症患者免疫治疗的预后生物标志物和预测模型奠定了基础。
