Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy

Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment. Despite demonstrable progress, mostpatients fail to respond or achieve durable responses due to primary or acquired ICB resistance. Recently, tumor epithelial-tomesenchymal plasticity (EMP) was identified as a critical determinant in regulating immune escape and immunotherapy resistancein cancer. In this review, we summarize the emerging role of tumor EMP in ICB resistance and the tumor-intrinsic or extrinsicmechanisms by which tumors exploit EMP to achieve immunosuppression and immune escape. We discuss strategies to modulatetumor EMP to alleviate immune resistance and to enhance the efficiency of ICB therapy. Our discussion provides new prospects toenhance the ICB response for therapeutic gain in cancer patients.