Targeting Autophagy-Immune Crosstalk: Dual Inhibition of ATG7 and Checkpoint Pathways in Immunotherapy-Resistant Cancers

Zhang et al. (2024, J Exp Clin Cancer Res) showed that ATG7 inhibition boosts MHC-I expression and immune infiltration in MSI-H colorectal cancer, enhancing checkpoint inhibitor sensitivity. Extending this, one could test whether ATG7 inhibition can “heat up” immunologically cold cancers (like MSS CRC or certain breast/prostate tumors) that typically resist checkpoint therapy. This dual-target approach could be evaluated in preclinical models and, if promising, in early-phase clinical trials. The novelty is the focus on cancers not usually considered for immunotherapy, aiming to break through historical barriers to checkpoint efficacy.

References:

1. Inhibition of autophagy-related protein 7 enhances anti-tumor immune response and improves efficacy of immune checkpoint blockade in microsatellite instability colorectal cancer. Wenxin Zhang, Lu Chen, Jiafeng Liu, Bicui Chen, Huanying Shi, Haifei Chen, H. Qi, Zi-Qian Wu, Xiang Mao, Xinhai Wang, Yuxin Huang, Jiyifan Li, Zheng Yu, Mingkang Zhong, Tianxiao Wang, Qunyi Li (2024). Journal of experimental & clinical cancer research : CR.