每个哺乳动物细胞表面MHC（主要组织相容性复合物）或HLA（人类白细胞抗原）系统内天然呈现肽的曲目被称为配体组或免疫肽组，并在CD8 + T细胞能够识别和杀死以MHC-I抗原限制方式出现的癌细胞的发现后获得了动力。事实上，癌症免疫监视依赖于T细胞对MHC-I限制的肽的识别，使得确定这些肽成为设计基于T细胞的癌症疫苗的核心。此外，靶向免疫检查点分子的抗体的突破已经引起了寻找适合CD8 + T细胞的治疗靶点的新兴趣。治疗性癌症疫苗旨在人工生成和/或刺激CD8 + T细胞，因此与ICI结合以释放免疫系统中断的自然后果来增强抗肿瘤效果。在这种情况下，识别和了解肽候选者的知识利用免疫肽组和质谱方法的快速技术更新的优势，为设计免疫治疗方法的疫苗铺平了道路。在本综述中，我们主要讨论免疫肽组分析的作用及其在生成以HLA-I肽为主要焦点的治疗性癌症疫苗方面的应用。在这里，我们回顾基于两种不同准备方法的癌症疫苗平台：病原体（病毒和细菌）和非病原体（VLP、纳米颗粒、亚单位疫苗），利用配体组领域的发现来生成和/或增强抗肿瘤特异性反应。最后，我们讨论了该领域可能遇到的可能缺点和未来挑战。版权所有©2023作者。由Elsevier出版。保留所有权利。

The repertoire of naturally presented peptides within the MHC (major histocompatibility complex) or HLA (human leukocyte antigens) system on the cellular surface of every mammalian cell is referred to as ligandome or immunopeptidome. This later gained momentum upon the discovery of CD8 + T cells able to recognize and kill cancer cells in an MHC-I antigen-restricted manner. Indeed, cancer immune surveillance relies on T cell recognition of MHC-I-restricted peptides, making the identification of those peptides the core for designing T cell-based cancer vaccines. Moreover, the breakthrough of antibodies targeting immune checkpoint molecules has led to a new and strong interest in discovering suitable targets for CD8 +T cells. Therapeutic cancer vaccines are designed for the artificial generation and/or stimulation of CD8 +T cells; thus, their combination with ICIs to unleash the breaks of the immune system comes as a natural consequence to enhance anti-tumor efficacy. In this context, the identification and knowledge of peptide candidates take advantage of the fast technology updates in immunopeptidome and mass spectrometric methodologies, paying the way to the rational design of vaccines for immunotherapeutic approaches. In this review, we discuss mainly the role of immunopeptidome analysis and its application for the generation of therapeutic cancer vaccines with main focus on HLA-I peptides. Here, we review cancer vaccine platforms based on two different preparation methods: pathogens (viruses and bacteria) and not (VLPs, nanoparticles, subunits vaccines) that exploit discoveries in the ligandome field to generate and/or enhance anti-tumor specific response. Finally, we discuss possible drawbacks and future challenges in the field that remain still to be addressed.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.