Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Clínica Médica - Rio de Janeiro (RJ), Brazil.
Instituto Nacional de Saúde da Mulher, Criança e do Adolescente Fernandes Figueira - Rio de Janeiro (RJ), Brazil.
Rev Assoc Med Bras (1992). 2023 Sep 18;69(9):e20230276. doi: 10.1590/1806-9282.20230276. eCollection 2023.
Tumor-infiltrating lymphocytes are detectable in up to 75% of triple-negative breast cancer. The composition of these infiltrates may influence prognosis and is not known regarding regulatory or effector lymphocytes. The objectives of this study were to describe and quantify the composition of the tumor-infiltrating lymphocytes before and after chemotherapy (neoadjuvant chemotherapy) and to evaluate their association with complete pathological response and overall survival.
This was a retrospective observational study. Clinical and pathological data from 38 triple-negative breast cancer patients treated with neoadjuvant chemotherapy at the University Hospital (HUCFF/UFRJ), between November 2004 and November 2018, were analyzed. The Stromal tumor-infiltrating lymphocytes (Stromal tumor-infiltrating lymphocytes) have been identified on hematoxylin and eosin-stained sections according to the guidelines of the "International tumor-infiltrating lymphocytes Working Group." Immunohistochemistry studies were performed to identify T-cell subsets (i.e., CD3, CD4, CD8, and FOXP3) and T-cell exhaustion (i.e., programmed cell death protein 1).
Statistically significant changes in stromal tumor-infiltrating lymphocyte categories were observed before and post-neoadjuvant chemotherapy, with 32% of intermediate cases becoming high. The correlation between pre-neoadjuvant chemotherapy stromal tumor-infiltrating lymphocytes and pathological response, pre-neoadjuvant chemotherapy and post-neoadjuvant chemotherapy, and stromal tumor-infiltrating lymphocytes and overall survival was not statistically significant. However, we noticed an increase of cells that favor the antitumor activity (i.e., CD3, CD8, and CD8/FOXP3 ratio) and decreased levels of cells inhibiting tumor activities (i.e., FOXP3 and programmed cell death protein 1) post-neoadjuvant chemotherapy. Importantly, programmed cell death protein 1 expression pre-neoadjuvant chemotherapy showed an association with pathological response.
In this study, we observed that chemotherapy significantly increases stromal tumor-infiltrating lymphocytes, CD8 T cells, as well as CD8/FoxP3 ratio. Most importantly, programmed cell death protein 1 expression before neoadjuvant chemotherapy positively correlates with pathological response suggesting the use of programmed cell death protein 1 as a prognostic marker before neoadjuvant chemotherapy.
在多达 75%的三阴性乳腺癌中可检测到肿瘤浸润淋巴细胞。这些浸润物的组成可能影响预后，但关于调节性或效应性淋巴细胞的组成尚不清楚。本研究的目的是描述和量化化疗（新辅助化疗）前后肿瘤浸润淋巴细胞的组成，并评估其与完全病理缓解和总生存的关系。
这是一项回顾性观察性研究。分析了 2004 年 11 月至 2018 年 11 月期间在里约热内卢联邦大学附属医院（HUCFF/UFRJ）接受新辅助化疗的 38 例三阴性乳腺癌患者的临床和病理数据。根据“国际肿瘤浸润淋巴细胞工作组”的指南，在苏木精和伊红染色切片上识别基质肿瘤浸润淋巴细胞（基质肿瘤浸润淋巴细胞）。进行免疫组织化学研究以鉴定 T 细胞亚群（即 CD3、CD4、CD8 和 FOXP3）和 T 细胞耗竭（即程序性细胞死亡蛋白 1）。
新辅助化疗前后基质肿瘤浸润淋巴细胞分类有统计学意义的变化，中间病例中有 32%变为高。新辅助化疗前基质肿瘤浸润淋巴细胞与病理反应、新辅助化疗前与新辅助化疗后以及基质肿瘤浸润淋巴细胞与总生存之间无统计学相关性。然而，我们注意到新辅助化疗后有利于抗肿瘤活性的细胞（即 CD3、CD8 和 CD8/FOXP3 比值）增加，而抑制肿瘤活性的细胞（即 FOXP3 和程序性细胞死亡蛋白 1）水平降低。重要的是，新辅助化疗前程序性细胞死亡蛋白 1 的表达与病理反应有关。
在这项研究中，我们观察到化疗显著增加了基质肿瘤浸润淋巴细胞、CD8 T 细胞和 CD8/FOXP3 比值。最重要的是，新辅助化疗前程序性细胞死亡蛋白 1 的表达与病理反应呈正相关，这表明在新辅助化疗前使用程序性细胞死亡蛋白 1 作为预后标志物。
