研究动态
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程序性细胞死亡蛋白1是三阴性乳腺癌新辅助化疗反应的标志物。

Programmed cell death protein 1 is a marker for neoadjuvant chemotherapy response in triple-negative breast cancer.

发表日期:2023
作者: Maria de Fátima Dias Gaui, Luis Claudio Amendola, Danielle Carvalho Quintella, Nathalie Canedo, Adriana Bonomo
来源: Cell Death & Disease

摘要:

肿瘤浸润淋巴细胞(Tumor-infiltrating lymphocytes,简称TILs)在三阴性乳腺癌中可检测到,高达75%。这些浸润物的成分可能影响预后,目前对调节性或效应性淋巴细胞的情况尚不清楚。本研究的目标是描述和量化肿瘤浸润淋巴细胞在化疗前后(新辅助化疗)的组成,并评估其与完全病理反应和总体生存的关联。本研究为回顾性观察性研究,分析了2004年11月至2018年11月期间在大学医院(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”的指导方针,在苏木精和伊红染色的切片上识别出间质肿瘤浸润淋巴细胞(Stromal tumor-infiltrating lymphocytes)。进行免疫组化研究以鉴定T细胞亚群(如CD3、CD4、CD8和FOXP3)和T细胞耗竭(如程序性细胞死亡蛋白1)。在新辅助化疗前后观察到间质肿瘤浸润淋巴细胞类别发生了显著变化,32%的中等病例变为高度。新辅助化疗前和新辅助化疗后间质肿瘤浸润淋巴细胞、新辅助化疗前和新辅助化疗后以及间质肿瘤浸润淋巴细胞与总体生存之间的相关性均无统计学意义。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比率)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)的水平下降。重要的是,新辅助化疗前程序性细胞死亡蛋白1的表达与病理反应存在关联。在本研究中,我们观察到化疗显著增加了间质肿瘤浸润淋巴细胞、CD8 T细胞以及CD8/FoxP3比率。最重要的是,新辅助化疗前的程序性细胞死亡蛋白1表达与病理反应呈正相关,提示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。
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.