Jiajia Zhou, Ilona Kryczek, Shasha Li, Xiong Li, Angelo Aguilar, Shuang Wei, Sara Grove, Linda Vatan, Jiali Yu, Yijian Yan, Peng Liao, Heng Lin, Jing Li, Gaopeng Li, Wan Du, Weichao Wang, Xueting Lang, Weimin Wang, Shaomeng Wang, Weiping Zou
Targeting the p53-MDM2 pathway to reactivate tumor p53 is a chemotherapeutic approach. However, the involvement of this pathway in CD8+ T cell-mediated antitumor immunity is unknown. Here, we report that mice with MDM2 deficiency in T cells exhibit accelerated tumor progression and a decrease in tumor-infiltrating CD8+ T cell survival and function. Mechanistically, MDM2 competes with c-Cbl for STAT5 binding, reduces c-Cbl-mediated STAT5 degradation and enhances STAT5 stability in tumor-infiltrating CD8+ T cells...
April 2021: Nature Immunology