MHC class II expression influences the composition and distribution of immune cells in the metastatic colorectal cancer microenvironment Journal Article
| Authors: | Griffith, B. D.; Turcotte, S.; Lazarus, J.; Lima, F.; Bell, S.; Delrosario, L.; McGue, J.; Krishnan, S.; Oneka, M. D.; Nathan, H.; Smith, J. J.; D’Angelica, M. I.; Shia, J.; Di Magliano, M. P.; Rao, A.; Frankel, T. L. |
| Article Title: | MHC class II expression influences the composition and distribution of immune cells in the metastatic colorectal cancer microenvironment |
| Abstract: | Despite advances in therapy over the past decades, metastatic colorectal cancer (mCRC) remains a highly morbid disease. While the impact of MHC-I on immune infiltration in mCRC has been well studied, data on the consequences of MHC-II loss are lacking. Multiplex fluorescent immunohistochemistry (mfIHC) was performed on 149 patients undergoing curative intent resection for mCRC and stratified into high and low human leukocyte antigen isotype DR (HLA-DR) expressing tumors. Intratumoral HLA-DR expression was found in stromal bands, and its expression level was associated with different infiltrating immune cell makeup and distribution. Low HLA-DR expression was associated with increased intercellular distances and decreased population mixing of T helper cells and antigen-presenting cells (APC), suggestive of decreased interactions. This was associated with less co-localization of tumor cells and cytotoxic T lymphocytes (CTLs), which tended to be in a less activated state as determined by Ki67 and granzyme B expression. These findings suggest that low HLA-DR in the tumor microenvironment of mCRC may reflect a state of poor helper T-cell interactions with APCs and CTL-mediated anti-tumor activity. Efforts to restore/enhance MHC-II presentation may be a useful strategy to enhance checkpoint inhibition therapy in the future. © 2022 by the authors. |
| Keywords: | colon cancer; immuno-oncology; multiplex immunohistochemistry |
| Journal Title: | Cancers |
| Volume: | 14 |
| Issue: | 17 |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Date Published: | 2022-09-01 |
| Start Page: | 4092 |
| Language: | English |
| DOI: | 10.3390/cancers14174092 |
| PROVIDER: | scopus |
| PMCID: | PMC9454847 |
| PUBMED: | 36077630 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |
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