Possible involvement of intratumoral androgens in breast cancer immune microenvironment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07410
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Tohoku University
• Principal Investigator: TAKAGI Kiyoshi 東北大学, 医学系研究科, 准教授 (80595562)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 乳癌 / アンドロゲン / 腫瘍免疫

Outline of Final Research Achievements

We addressed the possible regulation of lymphocyte infiltration in breast cancer tissues by locally produced androgens. By immunohistochemical analyses, we demonstrated that immunoreactivity of androgen receptor (AR) was inversely correlated with CD3-positive T cell infiltration. This dtendency was apparent especially in the cases positive for 5alpha-reductase type 1 (5alpha Red1), an androgen-producing enzyme. On the other hand, 5alpha Red1 itself showed no correlation between lymphocyte infiltration in breast cancer tissues.
These findings suggested that locally produced androgens might induce the genes which regulated T cell infiltration and then caused decreased T cell infiltration in human breast cancer tissues.

Free Research Field

病理学、乳腺腫瘍学

Academic Significance and Societal Importance of the Research Achievements

乳癌は代表的な性ホルモン依存性腫瘍であるが、乳癌における男性ホルモン（アンドロゲン）の役割は未だ十分に解明されていない。我々は今回、腫瘍免疫という観点から乳癌におけるアンドロゲン作用を病理学的に解析し、アンドロゲンが乳癌組織のリンパ球浸潤を負に制御する可能性を見出した。腫瘍組織に浸潤するリンパ球を賦活化するがん免疫療法の発展が目覚ましい今日において、本研究は乳癌におけるがん免疫療法の奏功性の予測に貢献するものと考えられた。