Yuan Jiang, Yueyuan Zheng, Yuan-Wei Zhang, Shuai Kong, Jinxiu Dong, Fei Wang, Benjamin Ziman, Sigal Gery, Jia-Jie Hao, Dan Zhou, Jianian Zhou, Allen S Ho, Uttam K Sinha, Jian Chen, Shuo Zhang, Chuntong Yin, Dan-Dan Wei, Masaharu Hazawa, Huaguang Pan, Zhihao Lu, Wen-Qiang Wei, Ming-Rong Wang, H Phillip Koeffler, De-Chen Lin, Yan-Yi Jiang
Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively...
March 20, 2024: Nature Communications