Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment Journal Article
| Authors: | Gabel, A. M.; Crosse, E. I.; Belleville, A. E.; Hogg, S. J.; McKellar, S. A.; Abdel-Wahab, O.; Thomas, J. D.; Bradley, R. K. |
| Article Title: | Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment |
| Abstract: | Exploiting the immune system to eradicate cancer cells is an area of intense clinical study. However, the mechanisms that shape the tumor-immune microenvironment are incompletely understood. Here, we identify Muscleblind-like (MBNL) proteins as novel modulators of the tumor-immune microenvironment across diverse cancers. We demonstrate that loss of tumor MBNL expression results in an attenuated response to interferon gamma and reduced tumor antigen presentation in melanoma, breast cancer, and colorectal cancer cells. Parallel experiments in a syngeneic mouse melanoma model revealed that MBNL loss reduces tumor cell killing by CD8 + T cells in vitro and facilitates tumor escape from cytotoxic CD8 + T cell infiltration in vivo. Finally, we extended these studies to 29 human cancer types to find that MBNL expression levels are strongly associated with gene expression signatures of T cell tumor infiltration. These insights suggest that MBNL proteins play important roles in shaping the immune landscape across diverse malignancies. © 2025 Gabel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | immunohistochemistry; adult; controlled study; unclassified drug; human cell; genetics; nonhuman; flow cytometry; neoplasm; neoplasms; colorectal cancer; cd3 antigen; cd8 antigen; cd8+ t lymphocyte; cd8-positive t-lymphocytes; mouse; animal; metabolism; animals; mice; animal tissue; cell viability; gene; melanoma; breast cancer; gene expression; cell infiltration; animal experiment; animal model; antineoplastic activity; pathology; cell line, tumor; tumor antigen; mice, inbred c57bl; c57bl mouse; rna binding protein; gene expression regulation; rna-binding proteins; gene expression regulation, neoplastic; antigen presentation; immunology; gamma interferon; tumor cell line; western blotting; interferon-gamma; cytotoxicity assay; tumor microenvironment; peptides and proteins; tumor escape; gene ontology; muscleblind like protein; humans; human; male; female; article; receptor type tyrosine protein phosphatase c; b2m gene; b16-f10 cell line; eo771 cell line; cd8a gene; mbnl1 gene; mbnl2 gene |
| Journal Title: | PLoS ONE |
| Volume: | 20 |
| Issue: | 4 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2025-04-30 |
| Start Page: | e0321148 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0321148 |
| PUBMED: | 40305509 |
| PROVIDER: | scopus |
| PMCID: | PMC12043120 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
