Centre for Advanced Biotherapeutics and Regenerative Medicine, FAHS, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, India.
Department of Psychiatry, Washington university School of Medicine, St louis, MO, United States.
Int Rev Cell Mol Biol. 2024;389:104-152. doi: 10.1016/bs.ircmb.2024.05.001. Epub 2024 Jun 4.
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.
三阴性乳腺癌（TNBC）因其侵袭性和有限的治疗选择而带来重大的临床挑战。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针对 TNBC 的靶向免疫治疗策略和疫苗提供了一个很有前途的途径。DDR 是一个旨在维持基因组完整性的细胞机制的复杂网络。在 TNBC 中，遗传不稳定性是一个标志，DDR 组件的失调在肿瘤发生和进展中起着关键作用。这篇综述探讨了 DDR 和新抗原之间的复杂关系，揭示了 TNBC 细胞的潜在弱点。新抗原源自癌细胞中的体细胞突变，代表可以被免疫系统识别的独特抗原。TNBC 的遗传不稳定性倾向导致突变负担增加，从而产生丰富的新抗原库。DDR 和新抗原在 TNBC 中的汇聚为免疫治疗靶向提供了一个独特的机会。免疫疗法通过利用免疫系统有选择性地靶向癌细胞，彻底改变了癌症治疗。DDR 相关的新抗原赋予 TNBC 独特的免疫原性，使其成为免疫治疗干预的理想靶点。这篇综述还探讨了各种免疫治疗模式，包括免疫检查点抑制剂（ICIs）、过继细胞疗法和癌症疫苗，这些模式利用 DDR 和新抗原相互作用来增强抗肿瘤免疫反应。此外，针对 DDR 相关新抗原开发疫苗的潜力为 TNBC 的预防和治疗策略开辟了新的前沿。针对 TNBC 个体突变景观量身定制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 中的汇聚为开发创新的免疫疗法和疫苗提供了强有力的理由。理解和靶向这些相互关联的过程可能为个性化和有效的干预铺平道路，为应对 TNBC 带来的挑战的患者带来新的希望。
