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.

Over the past 2 decades, remarkable advancements in the screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC) have led to improved patient outcomes. For the treatment of NSCLC with actionable gene mutations, tyrosine kinase inhibitors developed against EGFR, ALK, RET, BRAF, ROS1, NTRK, MET, and KRAS, exhibit substantial antitumor activity and have been incorporated into standard treatment regimens. Additionally, numerous novel therapies, including immunotherapy and antibody-drug conjugate therapy, have been found to benefit patients with NSCLC. This review summarizes current advancements in targeted therapy for NSCLC, according to a systematic search of the PubMed database and synthesis of cutting-edge findings presented at the 2024 American Society of Clinical Oncology Annual Meeting and 2024 World Conference on Lung Cancer.