DNA损伤反应与新抗原：三阴性乳腺癌免疫治疗与疫苗开发的有利靶点

三阴性乳腺癌（TNBC）因其侵袭性强、治疗选择有限而成为临床上的重大挑战。DNA损伤反应（DDR）机制与新抗原的出现之间的相互作用，为开发针对TNBC的靶向免疫策略和疫苗提供了有希望的途径。DDR是一个复杂的细胞机制网络，旨在维护基因组的完整性。在TNBC中，遗传不稳定性是其特征，DDR组分的失调在肿瘤发生和发展中起着关键作用。本综述探讨了DDR与新抗原之间的复杂关系，揭示了TNBC细胞潜在的脆弱性。新抗原由癌细胞的体细胞突变产生，代表着免疫系统可以识别的独特抗原。TNBC的基因组不稳定倾向导致突变负荷增加，从而产生丰富的新抗原库。DDR与新抗原的结合，为免疫治疗提供了独特的靶点。免疫治疗通过激活免疫系统，选择性攻击癌细胞，已革新癌症治疗。由DDR相关新抗原赋予的免疫原性，使其成为理想的免疫干预目标。本文还探讨了多种免疫治疗方式，包括免疫检查点抑制剂（ICIs）、过继细胞治疗和癌症疫苗，利用DDR与新抗原的相互作用增强抗肿瘤免疫反应。此外，开发针对DDR相关新抗原的疫苗，也为预防和治疗TNBC开辟了新前沿。基于个体突变谱设计疫苗，有望实现精准医疗。总之，DDR与新抗原的结合提供了开发创新免疫疗法和疫苗的合理基础。深入理解并靶向这些相互关联的过程，有望开辟个性化且有效的治疗途径，为TNBC患者带来新希望。

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.