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

Author:

Hanamura Toru,Kitano Shigehisa,Kagamu Hiroshi,Yamashita Makiko,Terao Mayako,Okamura Takuho,Kumaki Nobue,Hozumi Katsuto,Iwamoto Takayuki,Honda Chikako,Kurozumi Sasagu,Niikura Naoki

Abstract

AbstractBackgroundElucidating 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 ofESR1,PGR, andARwere 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.

Funder

Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan

The 2021 Tokai University School of Medicine Research Aid

Chugai Pharmaceutical Co. Ltd.

Publisher

Springer Science and Business Media LLC

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