免疫疗法对晚期肝细胞癌表现出潜在的疗效，但不幸的是，其临床益处常常被癌症适应性免疫抑制反应所抵消。揭示癌细胞逃避免疫监视的机制将有助于开发新的免疫治疗方法和联合治疗。在本文中，通过分析调节T细胞浸润高组和低组之间差异表达基因的转录因子，我们发现癌蛋白B细胞淋巴瘤6（BCL6）抑制肿瘤浸润T淋巴细胞的浸润和活化，因此与较差的T细胞浸润相关。临床结果。通过抗体缺失实验，我们进一步证明CD4 T细胞而非CD8 T细胞是Bcl6抑制促进HCC发展的主要淋巴细胞群。从机制上讲，BCL6 降低癌细胞促炎细胞因子和 T 淋巴细胞趋化因子（例如 IL6、IL1F6 和 CCL5）的表达。此外，BCL6 上调内皮细胞特异性分子 1 (ESM1)，可能通过 ICAM-1/LFA-1 信号通路抑制 T 淋巴细胞的募集和激活。我们的研究结果揭示了癌细胞衍生的 BCL6 如何协助癌细胞免疫逃避的一种未被重视的旁分泌机制，并强调了 CD4 T 细胞在 HCC 免疫监视中的作用。© 2024。作者。

Immunotherapy exhibited potential effects for advanced hepatocellular carcinoma, unfortunately, the clinical benefits are often countered by cancer adaptive immune suppressive response. Uncovering the mechanism how cancer cells evade immune surveillance would help to develop new immunotherapy approaches and combination therapy. In this article, by analyzing the transcriptional factors which modulate the differentially expressed genes between T cell infiltration high group and low group, we identified oncoprotein B cell lymphoma 6 (BCL6) suppresses the infiltration and activation of tumor infiltrating T lymphocytes, thus correlated with poorer clinical outcome. By using antibody deletion experiment, we further demonstrated that CD4+T cells but not CD8+T cells are the main lymphocyte population suppressed by Bcl6 to promote HCC development. Mechanistically, BCL6 decreases cancer cell expression of pro-inflammatory cytokines and T lymphocyte chemokines such as IL6, IL1F6, and CCL5. Moreover, BCL6 upregulates Endothelial cell-specific molecule 1 (ESM1) to inhibit T lymphocyte recruitment and activation possibly through ICAM-1/LFA-1 signaling pathway. Our findings uncovered an unappreciated paracrine mechanism how cancer cell-derived BCL6 assists cancer cell immune evasion, and highlighted the role of CD4+T cells in HCC immune surveillance.© 2024. The Author(s).