Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Eur Rev Med Pharmacol Sci. 2021 Apr;25(7):2885-2897. doi: 10.26355/eurrev_202104_25542.
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers, and its poor response to treatment has been a major problem in the field of breast cancer. In recent years, the application of immune checkpoint inhibitors has introduced a new era of treatment. The IMpassion 130 trial used PD-L1 as a mature biomarker for immunotherapy in metastatic TNBC, but the population screened, which was only patients with positive PD-L1 expression, was too narrow. Otherwise, it could not be determined whether the PD-L1-positive group benefited from immunotherapy in early TNBC, but this was confirmed in the KEYNOTE-522 and IMpassion 031 studies, in which there was no significant difference in the benefit, whether patients were PD-L1-positive or not. Therefore, how to screen more suitable biomarkers for accurate immunotherapy has become a burning and persistent problem to be solved. In fact, immune infiltration has always been our focus in the process of exploring immunotherapy in TNBC, and tumor infiltrating lymphocytes (TILs) have been well-known for decades as a prognostic factor in early TNBC. Furthermore, TILs are positively correlated with both patient survival and pathological complete response (pCR) after neoadjuvant chemotherapy. Recently, increasingly more foundational experiments and clinical trial verifications suggest that TILs could contain more biomarkers. Thus, in this review, we will assess the composition and heterogeneity of TILs, their evaluation standards, their relationship with TNBC prognosis and the prediction ability of different treatment options in TNBC, and their correlation with other biomarkers in the clinical application. We also summarize new studies that show the future potential of TILs.
三阴性乳腺癌(TNBC)约占所有乳腺癌的 15-20%,其对治疗的反应较差一直是乳腺癌领域的一个主要问题。近年来,免疫检查点抑制剂的应用为治疗带来了新的时代。IMpassion 130 试验将 PD-L1 作为转移性 TNBC 免疫治疗的成熟生物标志物,但筛选的人群仅为 PD-L1 表达阳性的患者,范围太窄。否则,无法确定 PD-L1 阳性组在早期 TNBC 中是否从免疫治疗中获益,但 KEYNOTE-522 和 IMpassion 031 研究证实,无论患者 PD-L1 阳性与否,免疫治疗的获益没有差异。因此,如何筛选更适合免疫治疗的生物标志物已成为一个亟待解决的问题。事实上,免疫浸润一直是我们在 TNBC 探索免疫治疗过程中的关注焦点,肿瘤浸润淋巴细胞(TILs)作为早期 TNBC 的预后因素已被人们熟知数十年。此外,TILs 与患者生存和新辅助化疗后的病理完全缓解(pCR)呈正相关。最近,越来越多的基础实验和临床试验验证表明,TILs 可能包含更多的生物标志物。因此,在这篇综述中,我们将评估 TILs 的组成和异质性、其评估标准、与 TNBC 预后的关系以及在 TNBC 中不同治疗方案的预测能力,以及与临床应用中其他生物标志物的相关性。我们还总结了显示 TILs 未来潜力的新研究。