Supporting data for "Systemic Immune Biomarkers Reflect the Local Tumor Immune Environment in Recurrent/Metastatic Nasopharyngeal Carcinoma"

Changes within the tumor immune microenvironment (TME) are often reflected in peripheral immune populations. Therein, development of biomarkers based on peripheral immune population phenotypes offers an opportunity to capture intratumoral dynamics. Here in we report development of a peripheral immune-based biomarker approach for Nasopharyngeal Carcinoma (R/M NPC). We focused on quantitating levels of peripheral CX3CR1+ CD8+ T cells with high clonal similarity to tumor-infiltrating counterparts and expression of the exclusive CX3CR1 ligand CX3CL1 in NPC models. We found that NPC tumor cell expression of CX3CL1 impacted the stemness and immunoregulatory polarization of CX3CR1+CD8+ T cells while also promoting their infiltration into the TME. Analysis of peripheral blood collected from 38 R/M NPC patients treated a bifunctional fusion protein bintrafusp alfa demonstrated that responders retained stable immune profiles, while non-responders experienced a decrease in CX3CR1+CD8+ T cells and an increase in monocytic myeloid derived suppressor cells (M-MDSCs). Additionally, we observed a significant correlation between tissue PD-L1 expression status and levels of soluble immune checkpoints. These findings suggest that CX3CR1+CD8+ T cells may serve as a potential predictive biomarker for immunotherapeutic outcomes in NPC.

肿瘤免疫微环境（tumor immune microenvironment, TME）的动态变化常可在外周免疫细胞群中得到反映。基于外周免疫细胞群表型开发生物标志物，为捕捉瘤内免疫动态提供了可行途径。本研究针对复发/转移性鼻咽癌（Nasopharyngeal Carcinoma, R/M NPC），建立了一种基于外周免疫特征的生物标志物分析方法。我们聚焦于定量分析与肿瘤浸润同源细胞具有高克隆相似性的外周CX3CR1阳性CD8阳性T细胞，以及鼻咽癌模型中CX3CR1的特异性配体CX3CL1的表达水平。研究发现，鼻咽癌细胞CX3CL1的表达可影响CX3CR1+CD8+ T细胞的干细胞特性与免疫调节极化状态，同时促进其向肿瘤免疫微环境浸润。我们对38例接受双功能融合蛋白bintrafusp alfa治疗的复发/转移性鼻咽癌患者的外周血进行分析，结果显示，免疫治疗应答者的免疫谱保持稳定，而非应答者的CX3CR1+CD8+ T细胞水平下降，同时单核细胞源性髓系抑制细胞（monocytic myeloid derived suppressor cells, M-MDSCs）比例升高。此外，我们观察到组织PD-L1表达状态与可溶性免疫检查点水平存在显著相关性。上述研究结果表明，CX3CR1+CD8+ T细胞有望成为鼻咽癌免疫治疗疗效的潜在预测性生物标志物。