Neutralizing IL-38 activates γδ T cell-dependent antitumor immunity and sensitizes for chemotherapy.

ABSTRACT:

Background

The interleukin (IL)-1-family receptor antagonist IL-38 has emerged as a negative regulator of auto-inflammation. Given the intricate interplay between antitumor immunity and auto-inflammation, we hypothesized that blocking IL-38 may enhance tumor immune control.

Methods

Our hypothesis was tested in the transgenic polyoma virus middle T oncoprotein mammary carcinoma model that is suitable for identifying strong immunomodulators. To investigate the effect of acute IL-38 blockade, we used a neutralizing antibody, alone or in combination with chemotherapy. Immune cell composition and location in tumors were determined by flow cytometry and immunohistochemistry, respectively. The role of γδ T cells was studied using an antibody blocking γδ T-cell receptor signaling. W

SUBMITTER: da Silva P 

PROVIDER: S-EPMC11367332 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature