Intestinal estrogen receptor beta modulates the murine colon tumor immune microenvironment

Area of Science:

• Oncology
• Immunology
• Endocrinology

Background:

• Chronic inflammation is a key driver of colorectal cancer (CRC) development.
• Estrogen, particularly estrogen receptor beta (ERβ), shows protective effects against CRC, but its role in the tumor microenvironment is unclear.

Purpose of the Study:

• To investigate the role of intestinal ERβ in shaping the colorectal tumor microenvironment and antitumor immunity.
• To analyze gene expression and immune cell infiltration in wild-type and ERβ knockout mice models of CRC.

Main Methods:

• RNA sequencing of colonic epithelia and tumors from mice treated with azoxymethane/dextran sulfate sodium.
• Bioinformatic analysis of transcriptomic data, including gene expression and immune cell deconvolution.
• Immunostaining to assess immune cell infiltration in tumors.

Main Results:

• Significant differences in gene expression and immune-related biological processes were observed between wild-type and ERβ knockout mice.
• ERβ knockout tumors showed increased macrophage infiltration, decreased T cell infiltration, and impaired natural killer cell infiltration.
• ERβ mRNA levels in human CRC tumors correlated with immune signaling and improved patient survival.

Conclusions:

• Intestinal ERβ plays a crucial role in promoting an antitumor microenvironment.
• ERβ modulates immune cell infiltration, impacting antitumor immunity in colorectal cancer.
• ERβ represents a potential therapeutic target for enhancing immunotherapy effectiveness in CRC.