[摘 要] 肿瘤新抗原是肿瘤细胞特有的异常肽段，可被免疫系统识别，是精准肿瘤免疫治疗的研究热点。本文概述肿瘤新抗 原的多元分子起源，分析MHCⅠ/Ⅱ类分子的抗原加工与提呈机制，并探讨交叉提呈在免疫识别中的关键作用；分析T细胞受体 （TCR）复合体的结构与信号转导特征，强调免疫原性评估的重要性，阐述高通量组学及人工智能/深度学习在新抗原发现与 MHC-肽、TCR-肽-MHC相互作用预测中的进展。同时，介绍基于新抗原的治疗性疫苗和过继细胞疗法在实体瘤中的应用前景与 挑战，讨论新抗原预测局限性、肿瘤免疫逃逸及伦理问题，并展望单细胞空间转录组等技术对免疫治疗设计、TCR分子设计及全 球新抗原库构建的意义。

[Abstract] Tumor neoantigens are aberrant peptides unique to tumor cells, which can be recognized by the immune system and have become a research hotspot in precision tumor immunotherapy. This article provides an overview of the diverse molecular origins of tumor neoantigens, analyzes the antigen processing and presentation mechanisms of MHC class Ⅰ/Ⅱ molecules, and explores the critical role of cross-presentation in immune recognition. It also analyzes the structural and signal transduction characteristics of the T cell receptor (TCR) complex, emphasizes the importance of immunogenicity evaluation, and elaborates on the progress of high-throughput omics and artificial intelligence/deep learning in neoantigen discovery and the prediction of MHC-peptide and TCR-peptide-MHC interactions. Additionally, it introduces the application prospects and challenges of neoantigen-based therapeutic vaccines and adoptive cell therapy in solid tumors, discusses the limitations of neoantigen prediction, tumor immune escape, and ethical issues, and looks forward to the significance of technologies such as single-cell spatial transcriptomics for immunotherapy design, TCR molecular design, and the construction of a global neoantigen repository.

[基金项目] 中国博士后科学基金（No. 2023M730673）；国家自然科学基金重点项目（No.82130077）；国家科技重大专项 （No. 2023ZD0502000）