Tumor Plasticity and Resistance to Immunotherapy

Tumor cell plasticity in the context of an EMT has been implicated in resistance to immune checkpoint blockade (ICB). Novel drugs targeting drivers of tumor cell plasticity are able to sensitize tumors to immune-mediated lysis. Tumor cell plasticity-modulating drugs synergize with ICB therapy for more robust antitumor immunity. Novel drugs, including cancer vaccines, targeting EMT transcription factors show promising results and offer new options for patients. Tumor cell plasticity exhibited as an epithelial–mesenchymal transition (EMT) has been identified as a major obstacle for the effective treatment of many cancers. This process, which involves the dedifferentiation of epithelial tumor cells towards a motile, metastatic, and mesenchymal tumor phenotype, mediates resistance to conventional therapies and small-molecule targeted therapies. In this review, we highlight current research correlating the role of tumor plasticity with resistance to current immunotherapy approaches and discuss future and ongoing combination immunotherapy strategies to reduce tumor cell plasticity-driven resistance in cancer. Tumor cell plasticity exhibited as an epithelial–mesenchymal transition (EMT) has been identified as a major obstacle for the effective treatment of many cancers. This process, which involves the dedifferentiation of epithelial tumor cells towards a motile, metastatic, and mesenchymal tumor phenotype, mediates resistance to conventional therapies and small-molecule targeted therapies. In this review, we highlight current research correlating the role of tumor plasticity with resistance to current immunotherapy approaches and discuss future and ongoing combination immunotherapy strategies to reduce tumor cell plasticity-driven resistance in cancer.