Correlation study of tumor-infiltrating lymphocytes (TILs) and subtypes analysis before and after neoadjuvant chemotherapy in triple-negative breast cancer

三阴性乳腺癌新辅助化疗前后肿瘤浸润淋巴细胞(TILs)及其亚型分析的相关性研究

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Abstract

BACKGROUND: In recent years, neoadjuvant chemotherapy (NACT) has become an increasingly important treatment for triple-negative breast cancer (TNBC). As the most immunogenic subtype of breast cancer, it is imperative to comprehensively study the immune microenvironment of TNBC and the effects of NACT on it. Our study aims to address this need and provide valuable insights for the development of effective postoperative adjuvant treatment strategies. METHODS: Samples were taken prior to and following NACT with docetaxel, epirubicin, and cyclophosphamide (TEC) from 71 TNBC patients who were included in this trial. We examined the clinicopathological alterations in patients before and after NACT treatment, assessed the impact of stromal tumor-infiltrating lymphocytes (sTILs) and immune biomarkers [CD8, CD4, CD3, FOXP3, CD20, CD163, programmed cell death ligand 1 (PD-L1)] on the efficacy of neoadjuvant therapy, and identified changes in NACT-induced immune subsets and specific immune biomarkers. RESULTS: Our study revealed that tumor size, histological grade, Ki-67 status, and sTILs content in baseline clinical features, as well as CD3, CD4, and CD8 content before NACT, showed significant differences between pathological complete response (pCR) and non-pCR patients (P<0.05). The expression of sTILs and PD-L1 in residual lesions after NACT was found to be higher than before NACT. Univariate analysis indicated that the levels of sTILs, CD3, CD4, and CD8 immune subsets before NACT were correlated with pCR. Importantly, multivariate regression analysis demonstrated that sTILs and CD8 immune subsets before NACT served as independent predictors of TNBC neoadjuvant therapy (P<0.05), providing crucial insights into the individualized management of TNBC. CONCLUSIONS: The findings of this study suggest that increasing sTILs and CD8 can significantly enhance the neoadjuvant efficacy of TNBC. Furthermore, the addition of CD3 and CD8 immune subsets can substantially improve the efficacy of TNBC neoadjuvant prediction. The detection of relevant immune markers after neoadjuvant therapy holds great promise in providing more comprehensive and accurate prognostic and therapeutic information for TNBC patients.

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