三阴性乳腺癌（TNBC）由于其侵袭性和有限的治疗选择而带来了重大的临床挑战。 DNA 损伤反应 (DDR) 机制与新抗原的出现之间的相互作用为开发 TNBC 靶向免疫治疗策略和疫苗提供了一条有希望的途径。 DDR 是一个复杂的细胞机制网络，旨在维持基因组完整性。在以遗传不稳定性为标志的 TNBC 中，DDR 成分的失调在肿瘤发生和进展中发挥着关键作用。这篇综述探讨了 DDR 和新抗原之间的复杂关系，揭示了 TNBC 细胞的潜在脆弱性。由癌细胞体细胞突变产生的新抗原代表了可以被免疫系统识别的独特抗原。 TNBC 的基因组不稳定倾向导致突变负担增加，从而产生丰富的新抗原。 DDR 和新抗原在 TNBC 中的融合为免疫治疗靶向提供了独特的机会。免疫疗法通过利用免疫系统选择性地靶向癌细胞，彻底改变了癌症治疗。 TNBC 中 DDR 相关新抗原赋予的独特免疫原性使其成为免疫治疗干预的理想靶标。本综述还探讨了各种免疫治疗方式，包括免疫检查点抑制剂 (ICIs)、过继细胞疗法和癌症疫苗，它们利用 DDR 和新抗原的相互作用来增强抗肿瘤免疫反应。此外，开发针对 DDR 相关新抗原的疫苗的潜力为 TNBC 的预防和治疗策略开辟了新领域。针对 TNBC 个体突变状况的疫苗的合理设计为精准医学方法带来了希望。总之，DDR 和新抗原在 TNBC 中的融合为创新免疫疗法和疫苗的开发提供了令人信服的理由。了解并针对这些相互关联的过程可能会为个性化和有效的干预措施铺平道路，为应对 TNBC 带来的挑战的患者带来新的希望。版权所有 © 2024。由 Elsevier Inc. 出版。

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its aggressive nature and limited therapeutic options. The interplay between DNA damage response (DDR) mechanisms and the emergence of neoantigens represents a promising avenue for developing targeted immunotherapeutic strategies and vaccines for TNBC. The DDR is a complex network of cellular mechanisms designed to maintain genomic integrity. In TNBC, where genetic instability is a hallmark, dysregulation of DDR components plays a pivotal role in tumorigenesis and progression. This review explores the intricate relationship between DDR and neoantigens, shedding light on the potential vulnerabilities of TNBC cells. Neoantigens, arising from somatic mutations in cancer cells, represent unique antigens that can be recognized by the immune system. TNBC's propensity for genomic instability leads to an increased mutational burden, consequently yielding a rich repertoire of neoantigens. The convergence of DDR and neoantigens in TNBC offers a distinctive opportunity for immunotherapeutic targeting. Immunotherapy has revolutionized cancer treatment by harnessing the immune system to selectively target cancer cells. The unique immunogenicity conferred by DDR-related neoantigens in TNBC positions them as ideal targets for immunotherapeutic interventions. This review also explores various immunotherapeutic modalities, including immune checkpoint inhibitors (ICIs), adoptive cell therapies, and cancer vaccines, that leverage the DDR and neoantigen interplay to enhance anti-tumor immune responses. Moreover, the potential for developing vaccines targeting DDR-related neoantigens opens new frontiers in preventive and therapeutic strategies for TNBC. The rational design of vaccines tailored to the individual mutational landscape of TNBC holds promise for precision medicine approaches. In conclusion, the convergence of DDR and neoantigens in TNBC presents a compelling rationale for the development of innovative immunotherapies and vaccines. Understanding and targeting these interconnected processes may pave the way for personalized and effective interventions, offering new hope for patients grappling with the challenges posed by TNBCs.Copyright © 2024. Published by Elsevier Inc.