Andour Layla, Hagenaars Sophie C, Gregus Barbara, Tőkes Anna Mária, Karancsi Zsófia, Tollenaar Rob A E M, Kroep Judith R, Kulka Janina, Mesker Wilma E
Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
Virchows Arch. 2025 Mar;486(3):427-444. doi: 10.1007/s00428-025-04039-z. Epub 2025 Feb 4.
Previous literature extensively explored biomarkers to personalize treatment for breast cancer patients. The clinical need is especially high in patients with triple-negative breast cancer (TNBC) due to its aggressive nature and limited treatment modalities. This review aims to evaluate the value of tumor-infiltrating lymphocytes (TILs) and tumor-stroma ratio (TSR) as prognostic biomarkers in TNBC patients and assess their clinical potential. A literature search was conducted in PubMed, Embase, Emcare, Web of Science, and Cochrane Library. Papers comparing survival outcomes of TNBC patients with low/high or negative/positive TSR and immune cells were included. The most frequently mentioned subgroups of TILs were selected and reported in this review. Data from 43 articles on TILs and eight articles on TSR were included. Among TNBC patients, high CD8 expression was generally associated with better survival. Notable, the poor survival outcomes were related to high intra-tumoral PD-L1 expression, whereas high stromal PD-L1 expression more often was correlated with favorable outcomes. For the TSR, a high amount of stroma in the primary tumor of TNBC patients was consistently associated with worse survival. This review highlights that a high number of CD8-positive T-cells is a promising prognostic factor for TNBC patients. PD-L1 expression analyzed for intra-tumoral and stromal expression separately reports strong but contrasting information. Finally, the TSR shows potential to be an important prognostic marker, especially for TNBC patients. Utilizing both biomarkers, either on itself or combined, could enhance clinical decision-making and personalization of treatment.
以往的文献广泛探索了生物标志物，以为乳腺癌患者实现个性化治疗。三阴性乳腺癌（TNBC）患者的临床需求尤为迫切，因为其侵袭性强且治疗方式有限。本综述旨在评估肿瘤浸润淋巴细胞（TILs）和肿瘤间质比（TSR）作为TNBC患者预后生物标志物的价值，并评估其临床潜力。在PubMed、Embase、Emcare、Web of Science和Cochrane图书馆进行了文献检索。纳入了比较TSR和免疫细胞低/高或阴性/阳性的TNBC患者生存结果的论文。本综述选择并报告了最常提及的TILs亚组。纳入了43篇关于TILs的文章和8篇关于TSR的文章的数据。在TNBC患者中，高CD8表达通常与更好的生存相关。值得注意的是，生存结果较差与肿瘤内PD-L1高表达有关，而基质PD-L1高表达更常与良好结果相关。对于TSR，TNBC患者原发性肿瘤中大量的间质一直与较差的生存相关。本综述强调，大量CD8阳性T细胞是TNBC患者有前景的预后因素。分别分析肿瘤内和基质中PD-L1表达报告了强烈但相反的信息。最后，TSR显示出成为重要预后标志物的潜力，尤其是对于TNBC患者。单独或联合使用这两种生物标志物都可以加强临床决策和治疗的个性化。
