摘要Malignant tumors are a major threat to human health with the immune responses critically influenced by major histocompatibility complex(MHC)class Ⅰ and Ⅱ molecules.While MHC-Ⅰ has been extensively studied for its role in tumor immunity,research on MHC-Ⅱ,particularly MHC-Ⅱ function within the tumor microenvironment,has lagged behind research on MHC-I.The expression and regulation of tumor-specific MHC-Ⅱ(tsMHC-Ⅱ)in tumor cells not only reflect the immunogenic landscape of the tumor microenvironment but also actively shape antitumor immune responses by modulating CD4+T cell recognition and activation.Expression of tsMHC-Ⅱ is tightly controlled by intrinsic oncogenic signaling and extrinsic cytokine stimulation,positioning tsMHC-Ⅱ as a key determinant of response to immunotherapy,including immune checkpoint blockade.Accordingly,tsMHC-Ⅱ may serve as a predictive biomarker and a potential therapeutic target in tumor immunotherapy.This review highlights recent advances in the structure and function of MHC-Ⅱ,the MHC-Ⅱ regulatory mechanisms in tumors,and the emerging significance of MHC-Ⅱ in guiding future immunotherapeutic strategies.