Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment.
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 a...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0321148 |
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| author | Austin M Gabel Edie I Crosse Andrea E Belleville Simon J Hogg Siegen A McKellar Omar Abdel-Wahab James D Thomas Robert K Bradley |
| author_facet | Austin M Gabel Edie I Crosse Andrea E Belleville Simon J Hogg Siegen A McKellar Omar Abdel-Wahab James D Thomas Robert K Bradley |
| author_sort | Austin M Gabel |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a373c28971e64c2c8b030d5e4e1c4049 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-a373c28971e64c2c8b030d5e4e1c40492025-08-20T02:50:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01204e032114810.1371/journal.pone.0321148Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment.Austin M GabelEdie I CrosseAndrea E BellevilleSimon J HoggSiegen A McKellarOmar Abdel-WahabJames D ThomasRobert K BradleyExploiting 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.https://doi.org/10.1371/journal.pone.0321148 |
| spellingShingle | Austin M Gabel Edie I Crosse Andrea E Belleville Simon J Hogg Siegen A McKellar Omar Abdel-Wahab James D Thomas Robert K Bradley Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment. PLoS ONE |
| title | Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment. |
| title_full | Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment. |
| title_fullStr | Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment. |
| title_full_unstemmed | Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment. |
| title_short | Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment. |
| title_sort | muscleblind like proteins are novel modulators of the tumor immune microenvironment |
| url | https://doi.org/10.1371/journal.pone.0321148 |
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