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中国乳腺癌患者分子亚型中CD4和CD8耗竭性肿瘤浸润淋巴细胞的分布

Distribution of CD4 and CD8 exhausted tumor-infiltrating lymphocytes in molecular subtypes of Chinese breast cancer patients.

作者信息

Shi Feng, Chang Hong, Zhou Quan, Zhao Yan-Jie, Wu Guang-Jiang, Song Qing-Kun

机构信息

Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People's Republic of China,

Department of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People's Republic of China.

出版信息

Onco Targets Ther. 2018 Sep 21;11:6139-6145. doi: 10.2147/OTT.S168057. eCollection 2018.

Abstract

PURPOSE

Breast cancer (BC) is the leading cancer affecting Chinese women; however, the immune microenvironment between molecular subtypes is less reported. This study aimed to investigate the distribution of tumor-infiltrating lymphocyte (TIL) subpopulations, especially exhausted CD4 and CD8 TILs in Chinese BC patients.

PATIENTS AND METHODS

A total of 133 patients with breast invasive ductal carcinoma were recruited consecutively from January 1, 2012 to December 31, 2013, and TILs were detected in H&E-stained sections. Expression profiling of PD-1, CD4, and CD8 was determined by immunohistochemistry on 4 µm formalin-fixed paraffin-embedded tissue sections. The distribution of TILs was analyzed based on hormone receptor status and molecular subtypes.

RESULTS

PD-1, CD4, and CD8 TILs distributed differently based on molecular subtypes. Compared to Luminal A, triple-negative breast cancer (TNBC) patients had more PD-1 TILs (39/high-power field [HPF] vs 11/HPF), PD-1 helper T (CD4) cells (28/HPF vs 10/HPF), and PD-1 cytotoxic (CD8) T-cells (3/HPF vs 2/HPF).

CONCLUSION

TILs are distributed differently based on molecular subtypes. TNBC patients exhibit more PD-1 exhausted TILs, representing an inhibitory immune microenvironment. PD-1/PD-L1 pathway is a potential therapeutic target of TNBC.

摘要

目的

乳腺癌是影响中国女性的主要癌症;然而,分子亚型之间的免疫微环境报道较少。本研究旨在调查中国乳腺癌患者肿瘤浸润淋巴细胞(TIL)亚群的分布,尤其是耗竭的CD4和CD8 TILs。

患者与方法

2012年1月1日至2013年12月31日连续招募了133例乳腺浸润性导管癌患者,并在苏木精-伊红(H&E)染色切片中检测TILs。通过免疫组织化学在4μm福尔马林固定石蜡包埋组织切片上测定PD-1、CD4和CD8的表达谱。根据激素受体状态和分子亚型分析TILs的分布。

结果

基于分子亚型,PD-1、CD4和CD8 TILs的分布不同。与Luminal A型相比,三阴性乳腺癌(TNBC)患者有更多的PD-1 TILs(39/高倍视野[HPF]对11/HPF)、PD-1辅助性T(CD4)细胞(28/HPF对10/HPF)和PD-1细胞毒性(CD8)T细胞(3/HPF对2/HPF)。

结论

基于分子亚型,TILs分布不同。TNBC患者表现出更多的PD-1耗竭TILs,代表一种抑制性免疫微环境。PD-1/PD-L1通路是TNBC的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deba/6160273/8ea8dd148f24/ott-11-6139Fig1.jpg

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