Emens Leisha A, Loi Sherene
Department of Medicine, University of Pittsburgh/UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania 15232, USA
Ankyra Therapeutics, Boston, Massachusetts 02116, USA.
Cold Spring Harb Perspect Med. 2023 Apr 3;13(4):a041332. doi: 10.1101/cshperspect.a041332.
Immunotherapy, particularly agents targeting the immunoregulatory PD-1/PD-L1 axis, harnesses the power of the immune system to treat cancer, with unique potential for a durable treatment effect due to immunologic memory. The PD-1 inhibitor pembrolizumab combined with neoadjuvant chemotherapy followed by adjuvant pembrolizumab improves event-free survival and is a new standard of care for high-risk, early-stage triple-negative breast cancer (TNBC), regardless of tumor PD-L1 expression. For metastatic TNBC, pembrolizumab combined with chemotherapy is a new standard of care for the first-line therapy of PD-L1 metastatic TNBC, with improvement in overall survival. The PD-L1 inhibitor atezolizumab combined with nab-paclitaxel is also approved outside the United States for the first-line treatment of metastatic PD-L1 TNBC. Current research focuses on refining the use of immunotherapy in TNBC by defining informative predictive biomarkers, developing immunotherapy in early and advanced HER2-driven and luminal breast cancers, and overcoming primary and secondary resistance to immunotherapy through unique immune-based strategies.
免疫疗法，尤其是针对免疫调节性PD-1/PD-L1轴的药物，利用免疫系统的力量来治疗癌症，由于免疫记忆，具有产生持久治疗效果的独特潜力。PD-1抑制剂帕博利珠单抗联合新辅助化疗，随后进行辅助性帕博利珠单抗治疗，可改善无事件生存期，并且是高危早期三阴性乳腺癌（TNBC）的一种新的治疗标准，无论肿瘤PD-L1表达情况如何。对于转移性TNBC，帕博利珠单抗联合化疗是PD-L1转移性TNBC一线治疗的新的治疗标准，可改善总生存期。PD-L1抑制剂阿替利珠单抗联合白蛋白结合型紫杉醇在美国境外也被批准用于转移性PD-L1 TNBC的一线治疗。当前的研究重点在于通过定义信息丰富的预测生物标志物来优化TNBC中免疫疗法的使用，在早期和晚期HER2驱动型和管腔型乳腺癌中开发免疫疗法，以及通过独特的基于免疫的策略克服对免疫疗法的原发性和继发性耐药性。
