南开大学曹雪涛研究团队发现，抑制癌细胞内的CD28增强抗肿瘤免疫并通过靶向PD-L1克服抗PD-1耐药性。相关论文于2024年12月12日在线发表在《癌细胞》杂志上。

附：英文原文

Title: Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1

Author: Zhen Yang, Xinpeng Liu, Jun Zhu, Yangyang Chai, Boyi Cong, Bo Li, Wanfeng Gao, Ye Hu, Mingyue Wen, Yanfang Liu, Li Fu, Xuetao Cao

Issue&Volume: 2024-12-12

Abstract: Deciphering mechanisms for cancer immune escape may provide targets for improving immunotherapy efficacy. By in vivo genome-wide CRISPR loss-of-function screening in a mouse model of triple negative breast cancer (TNBC), we uncovered a non-classical function of Cd28 in cancer cells to promote immune escape. Knocking out Cd28 in cancer cells increased infiltration of type I conventional DC (cDC1) and activated tumor-specific CD8+ T cells, and pharmaceutical inducible knockdown of Cd28 inhibited pre-established tumor growth and overcame anti-PD-1 resistance in vivo. Furthermore, high expression of cancer cell CD28 in human TNBC tissues correlated with elevated PD-L1 expression, less CD8+ T cell infiltration, and poor prognosis. Mechanistically, intracellular CD28 directly bound to Cd274 mRNA and recruited spliceosomal factor SNRPB2 to stabilize Cd274 mRNA in nucleus, promoting PD-L1 expression and immune escape. Therefore, disrupting cancer cell CD28-mediated immune escape may provide a potential approach to improve breast cancer immunotherapy.

DOI: 10.1016/j.ccell.2024.11.008

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00443-4