Expression of hormone receptors is associated with specific immunological profiles of the breast cancer microenvironment

Breast Cancer Research

Research

Takayuki Iwamoto¹  Takuho Okamura²  Mayako Terao²  Toru Hanamura²  Naoki Niikura²  Sasagu Kurozumi³  Chikako Honda⁴  Katsuto Hozumi⁵  Nobue Kumaki⁶  Makiko Yamashita⁷  Shigehisa Kitano⁷  Hiroshi Kagamu⁸ 

[1] Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, 700-8558, Kitaku, Okayama Prefecture, Japan;Department of Breast Oncology, Tokai University School of Medicine, 143 Shimokasuya, 259-1193, Isehara-shi, Kanagawa Prefecture, Japan;Department of Breast Surgery, International University of Health and Welfare, 4-3, Kozunomori, 286-8686, Narita-shi, Chiba Prefecture, Japan;Department of General Surgical Science, Gunma University Graduate School of Medicine, 39-22, Showa-machi 3-chome, 371-8511, Maebashi-shi, Gunma Prefecture, Japan;Department of Immunology, Tokai University School of Medicine, 143 Shimokasuya, 259-1193, Isehara-Shi, Kanagawa Prefecture, Japan;Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, 259-1193, Isehara-shi, Kanagawa Prefecture, Japan;Division of Cancer Immunotherapy Development, Center for Advanced Medical Development, The Cancer Institute Hospital of JFCR, 3-8-31, Ariake, 135-8550, Koto, Tokyo, Japan;Division of Respiratory Medicine, Saitama Medical University International Medical Center, 1397-1, Yamane, 350-1298, Hidaka-shi, Saitama Prefecture, Japan;

关键词: Breast cancer;    Estrogen receptor;    Progesterone receptor;    Androgen receptor;    Tumor immunity;    Microenvironment;    Immune cell composition;   

DOI  :  10.1186/s13058-023-01606-7

 received in 2022-07-11, accepted in 2023-01-17,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundElucidating the unique immunoregulatory mechanisms in breast cancer microenvironment may help develop new therapeutic strategies. Some studies have suggested that hormone receptors also have immune regulatory functions, but their mechanisms are not fully understood. In this study, we have comprehensively analyzed the relationship between the expressions of estrogen (ER), progesterone (PgR), and androgen receptors (AR), and the immunological profile in breast cancer.MethodsUsing publicly available gene expression profile datasets, METABRIC and SCAN-B, the associations between the expressions of hormone receptors and the immune cell compositions in breast cancer tissue, estimated by CIBERSORTx algorithm, were analyzed. We histologically evaluated tumor-infiltrating lymphocytes (hTIL), PD-L1 (hPD-L1) expression, and the infiltration of 11 types of immune cells by flow cytometry (FCM) for 45 breast cancer tissue samples. The relationships between them and the expressions of ER, PgR, and AR of tumor tissues, evaluated immunohistochemically, were analyzed.ResultsExpressions of ESR1, PGR, and AR were negatively correlated with overall immune composition. Expressions of ER and AR, but not that of PgR, were inversely associated with hTIL and hPD-L1 expression. FCM analysis showed that the expressions of ER and AR, but not that of PgR, were associated with decreased total leukocyte infiltration. Both CIBERSORTx and FCM analysis showed that ER expression was associated with reduced infiltration of macrophages and CD4+ T cells and that of AR with reduced macrophage infiltration.ConclusionHormone receptor expression correlates with specific immunological profiles in the breast cancer microenvironment both at the gene and protein expression levels.

【 授权许可】

CC BY   
© The Author(s) 2023

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