Das Kaushik, Paul Subhojit, Ghosh Arnab, Gupta Saurabh, Mukherjee Tanmoy, Shankar Prem, Sharma Anshul, Keshava Shiva, Chauhan Subhash C, Kashyap Vivek Kumar, Parashar Deepak
Department of Cellular and Molecular Biology, The University of Texas at Tyler Health Science Center, Tyler, TX 75708, USA.
School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700012, India.
Cancers (Basel). 2023 Oct 7;15(19):4879. doi: 10.3390/cancers15194879.
Triple-negative breast cancer (TNBC) is an aggressive subtype accounting for ~10-20% of all human BC and is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) amplification. Owing to its unique molecular profile and limited targeted therapies, TNBC treatment poses significant challenges. Unlike other BC subtypes, TNBC lacks specific molecular targets, rendering endocrine therapies and HER2-targeted treatments ineffective. The chemotherapeutic regimen is the predominant systemic treatment modality for TNBC in current clinical practice. However, the efficacy of chemotherapy in TNBC is variable, with response rates varying between a wide range of patients, and the emerging resistance further adds to the difficulties. Furthermore, TNBC exhibits a higher mutational burden and is acknowledged as the most immunogenic of all BC subtypes. Consequently, the application of immune checkpoint inhibition has been investigated in TNBC, yielding promising outcomes. Recent evidence identified extracellular vesicles (EVs) as an important contributor in the context of TNBC immunotherapy. In view of the extraordinary ability of EVs to transfer bioactive molecules, such as proteins, lipids, DNA, mRNAs, and small miRNAs, between the cells, EVs are considered a promising diagnostic biomarker and novel drug delivery system among the prospects for immunotherapy. The present review provides an in-depth understanding of how EVs influence TNBC progression, its immune regulation, and their contribution as a predictive biomarker for TNBC. The final part of the review focuses on the recent key advances in immunotherapeutic strategies for better understanding the complex interplay between EVs and the immune system in TNBC and further developing EV-based targeted immunotherapies.
三阴性乳腺癌（TNBC）是一种侵袭性亚型，占所有人类乳腺癌的10%-20%，其特征是缺乏雌激素受体（ER）、孕激素受体（PR）以及人表皮生长因子受体2（HER2）扩增。由于其独特的分子特征和有限的靶向治疗方法，TNBC的治疗面临重大挑战。与其他乳腺癌亚型不同，TNBC缺乏特定的分子靶点，这使得内分泌治疗和HER2靶向治疗无效。在当前临床实践中，化疗方案是TNBC主要的全身治疗方式。然而，化疗在TNBC中的疗效各不相同，不同患者的反应率差异很大，而且新出现的耐药性进一步增加了治疗难度。此外，TNBC表现出更高的突变负担，被认为是所有乳腺癌亚型中免疫原性最强的。因此，免疫检查点抑制在TNBC中的应用已得到研究，并取得了有前景的结果。最近的证据表明，细胞外囊泡（EVs）是TNBC免疫治疗中的一个重要因素。鉴于EVs具有在细胞间传递生物活性分子（如蛋白质、脂质、DNA、mRNA和小miRNA）的非凡能力，在免疫治疗前景中，EVs被认为是一种有前景的诊断生物标志物和新型药物递送系统。本综述深入探讨了EVs如何影响TNBC的进展、其免疫调节以及它们作为TNBC预测生物标志物的作用。综述的最后一部分重点介绍了免疫治疗策略的最新关键进展，以便更好地理解TNBC中EVs与免疫系统之间的复杂相互作用，并进一步开发基于EVs的靶向免疫疗法。
