Combination treatment with 17β-estradiol and anti-PD-L1 suppresses MC38 tumor growth by reducing PD-L1 expression and enhancing M1 macrophage population in MC38 colon tumor model. (1st September 2022)

• Record Type: Journal Article
• Authors: Song, Chin-Hee; Kim, Nayoung; Nam, Ryoung Hee; Choi, Soo In; Jang, Jae Young; Kim, Jin Won; Na, Hee Young; Lee, Ha-Na
• Is Part Of: Cancer letters. Volume 543(2022)
• Publication Date: 2022-09-01
• Subjects: Colon cancer -- Sex difference -- Programmed death-ligand 1 -- Immune checkpoint inhibitor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2022.215780
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: 17β-estradiol (E2) is known to have a protective effect in colorectal cancer (CRC); thus, E2 may be effective for cancer immunotherapy in CRC. The aim of this study is to evaluate the effect of combination therapy with E2 and anti-programmed cell death receptor-1 ligand (PD-L1) antibodies, and the effects of sex and estrogen on colon tumor growth, PD-L1 expression, and tumor-associated cell populations in an MC38 colon tumor model. Male mice showed increased MC38 colon tumor growth and PD-L1 expression in tumor sections as well as higher proportion of cancer-associated fibroblasts (CD45 − CD31 − CD140a + ), PD-L1-expressing tumor cells (CD45 − CD274 + ) and tumor-associated macrophages (TAMs) (CD11b + F4/80 + CD274 + ) compared to female mice. E2 treatment prior to MC38 injection significantly reduced these phenomena in male mice. Furthermore, co-treatment with E2 and anti-PD-L1 antibodies significantly inhibited MC38 tumor growth and reduced PD-L1-expressing cells in male mice compared to treatment with either E2 or anti-PD-L1 antibodies alone. Combination treatment with E2 and anti-PD-L1 decreased TAM population (CD11b + F4/80 + ) in the tumor mass while increasing M1 TMAs (CD11b + F4/80 + CD86 + ). These results suggest that estrogen inhibits MC38 tumor growth by downregulating PD-L1 expression and regulating tumor-associated cell populations. Furthermore, estrogen boosted the effect of anti-PD-L1 antibody in the MC38 tumor model. Highlights: 17β-estradiol is known to have a protective effect in colon cancer development. Sex differences exist in MC38 tumor growth, PD-L1 expression, and cell populations. 17β-estradiol treatment before MC38 injection reduced high cell types in males. Synergistic effect of 17β-estradiol on anti-tumorigenic effect of anti-PD-L1.