Liang Jiafeng, Zhu Lucheng, Li Jiawei, Wu Kan, Zhang Minna, Ma Shenglin, Chen Xueqin, Xia Bing
Department of Thoracic Oncology, Hangzhou Cancer Hospital, Hangzhou, 310002, China.
Discov Oncol. 2024 Sep 30;15(1):509. doi: 10.1007/s12672-024-01357-7.
Immunotherapy faces a major challenge in treatment resistance, highlighting the need for efficacy biomarkers identification. The tumor microenvironment (TME) significantly influences treatment outcomes, necessitating molecular TME exploration to address immunotherapy resistance.
The study initially pinpointed IL7R as a pivotal TME gene and then examined its impact on TME's CD8 + T cells at the single-cell level. Bulk-RNA analysis investigated IL7R function, immune cell infiltration related to IL7R in TCGA pan-cancer samples with its expression verified in clinical samples through immunohistochemistry. Genome instability and immune-related molecular expression associated with IL7R were also assessed. Furthermore, the clinical efficacy of IL7R was evaluated in various immunotherapy treatment cohorts.
Our single-cell analyses and cell-cased experiment revealed that T cells with high IL7R expression tended to be non-terminal and correlated with favorable immunotherapy responses. High IL7R expression corresponded to increased immune and stromal cell signiture, immune pathway enrichment, and an immune-inflamed environment in Bulk-RNA analysis and immunohistochemistry verification. These patients exhibited higher proportions of memory T cells and M1 cells within the TME, along with frequent genome instability and immune molecular upregulation. While IL7R had varied prognostic impact across the TCGA dataset, patients with high IL7R expression showed extended survival under immunotherapy.
IL7R plays a critical role in shaping TME diversity across cancer types and holds promise as a relevant biomarker for predicting immunotherapy benefits.
免疫疗法在治疗耐药性方面面临重大挑战，这凸显了识别疗效生物标志物的必要性。肿瘤微环境（TME）对治疗结果有显著影响，因此有必要对TME进行分子层面的探索以应对免疫疗法耐药性问题。
该研究首先将IL7R确定为关键的TME基因，然后在单细胞水平上研究其对TME中CD8 + T细胞的影响。批量RNA分析研究了IL7R的功能，通过免疫组化在临床样本中验证其表达后，分析了TCGA泛癌样本中与IL7R相关的免疫细胞浸润情况。还评估了与IL7R相关的基因组不稳定性和免疫相关分子表达。此外，在各种免疫疗法治疗队列中评估了IL7R的临床疗效。
我们的单细胞分析和细胞实验表明，高表达IL7R的T细胞往往不是终末细胞，且与良好的免疫疗法反应相关。在批量RNA分析和免疫组化验证中，高IL7R表达对应着免疫和基质细胞特征增加、免疫途径富集以及免疫炎症环境。这些患者的TME中记忆T细胞和M1细胞比例更高，同时基因组不稳定频繁且免疫分子上调。虽然IL7R在整个TCGA数据集中的预后影响各不相同，但高表达IL7R的患者在免疫疗法下生存期延长。
IL7R在塑造不同癌症类型的TME多样性方面起着关键作用，有望作为预测免疫疗法疗效的相关生物标志物。
