哈尔滨医科大学张学团队的一项最新研究发现CD160通过调节CD8⁺ T细胞耗竭在结直肠癌中影响抗PD-1免疫治疗耐药性。相关论文于2025年9月9日发表于国际顶尖学术期刊《Nature Cell Biology》杂志上。

通过比较结直肠癌（CRC）患者和健康供者的配对回肠和结肠样本，课题组研究人员发现了富含回肠的CD160⁺CD8⁺ T细胞具有以前未被识别的特征，包括抵抗终末衰竭和强克隆扩增。CD160⁺CD8⁺ T细胞的转移在微卫星不稳定性高和炎症诱导的CRC模型中显著抑制肿瘤的生长。CD160敲除加速肿瘤的生长，这可以通过转移Cd160 ⁺CD8⁺ T细胞来缓解。

值得注意的是，在微卫星不稳定性高和抗PD--1耐药的CRC模型中，CD160⁺CD8⁺ T细胞通过增加肿瘤浸润性祖衰竭T细胞来提高抗PD- -1的疗效并克服其耐药性，几乎可以根除肿瘤。在机制上，课题组发现CD160-PI3K （p85α）相互作用通过AKT-NF -κB途径促进FcεR1γ和4-1BB的表达，从而增强CD8⁺ T细胞的细胞毒性。他们的研究揭示了CD160是CD8⁺ T细胞功能的关键调节因子，并提出了一种创新的免疫治疗策略，即转移CD160⁺CD8⁺ T细胞来克服抗PD- -1耐药性。

据了解，结肠比回肠更容易发生肿瘤。然而，免疫微环境差异在导致这种差异中的作用尚不清楚。

附：英文原文

Title: CD160 dictates anti-PD-1 immunotherapy resistance by regulating CD8+ T cell exhaustion in colorectal cancer

Author: Zheng, Tongsen, Ding, Chujie, Lai, Shihui, Gao, Yang, Lyu, Cheng, Liu, Caiqi, Shi, Jiaqi, Li, Xiaobo, Li, Mingwei, Meng, Hongxue, Li, Mingqi, Liang, Yingjian, Tai, Sheng, Cheng, Liang, Zhang, Yan, Li, Li, Han, Peng, Sun, Bin, Liu, Te, Geng, Feng, Hao, Dapeng, Zhang, Xue

Issue&Volume: 2025-09-09

Abstract: The colon exhibits higher propensity for tumour development than ileum. However, the role of immune microenvironment differences in driving this disparity remains unclear. Here, by comparing paired ileum and colon samples from patients with colorectal cancer (CRC) and healthy donors, we identified ileum-enriched CD160+CD8+ T cells with previously unrecognized characteristics, including resistance to terminal exhaustion and strong clonal expansion. The transfer of CD160+CD8+ T cells significantly inhibits tumour growth in microsatellite instability-high and inflammation-induced CRC models. Cd160 knockout accelerates tumour growth, which is mitigated by transferring CD160+CD8+ T cells. Notably, in microsatellite instability-high and anti-PD-1-resistant CRC models, CD160+CD8+ T cells improve anti-PD-1 efficacy and overcome its resistance by increasing tumour-infiltrating progenitor-exhausted T cells, nearly eradicating tumours. Mechanistically, we uncover a CD160–PI3K (p85α) interaction that promotes FcεR1γ and 4-1BB expression via the AKT–NF-κB pathway, thereby enhancing CD8+ T cell cytotoxicity. Our study reveals CD160 as a crucial regulator of CD8+ T cell function and proposes an innovative immunotherapy strategy of transferring CD160+CD8+ T cells to overcome anti-PD-1 resistance.

DOI: 10.1038/s41556-025-01753-3

Source: https://www.nature.com/articles/s41556-025-01753-3