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Unlock the code of MHC II-enabled Cancer immunotherapy
Jiaqi Liu1, Xueru Song1, Wenqi Guo1
1Department of Medical Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China.
None:
Major Histocompatibility Complex class II (MHC II) molecules present tumor antigens to CD4 + T cells, playing a pivotal role in initiating anti-cancer immunity. Recent discoveries of MHC II expression on atypical antigen-presenting cells (APCs) have spurred interest in targeting MHC II for immunotherapy. Emerging therapies seek to enhance MHC II expression in tumors, particularly immunologically "cold" tumors with limited T-cell infiltration, to amplify CD4 + T cell-mediated anti-tumor responses. Clinical advances include MHC II-guided personalized vaccines, immune checkpoint blockade (ICB), and combination strategies showing promising efficacy. This review delineates MHC II-mediated immunoregulatory networks across professional and atypical APCs, explores their potential as biomarkers and therapeutic targets, and discusses predictive models of MHC II-antigen interactions to advance precision oncology. By elucidating the complexity of MHC II-driven immune regulation, this work aims to optimize immunotherapy design, address tumor heterogeneity, and foster tailored therapeutic approaches for diverse cancer types.
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