MHC Class II Expression Influences the Composition and Distribution of Immune Cells in the Metastatic Colorectal Cancer Microenvironment

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dc.citation.articleNumber4092en_US
dc.citation.issueNumber17en_US
dc.citation.journalTitleCancersen_US
dc.citation.volumeNumber14en_US
dc.contributor.authorGriffith, Brian D.en_US
dc.contributor.authorTurcotte, Simonen_US
dc.contributor.authorLazarus, Jennyen_US
dc.contributor.authorLima, Fatimaen_US
dc.contributor.authorBell, Samanthaen_US
dc.contributor.authorDelrosario, Lawrenceen_US
dc.contributor.authorMcGue, Jakeen_US
dc.contributor.authorKrishnan, Santhoshien_US
dc.contributor.authorOneka, Morgan D.en_US
dc.contributor.authorNathan, Harien_US
dc.contributor.authorSmith, J. Joshuaen_US
dc.contributor.authorD’Angelica, Michael I.en_US
dc.contributor.authorShia, Jinruen_US
dc.contributor.authorDi Magliano, Marina Pascaen_US
dc.contributor.authorRao, Arvinden_US
dc.contributor.authorFrankel, Timothy L.en_US
dc.date.accessioned2022-10-28T17:43:08Zen_US
dc.date.available2022-10-28T17:43:08Zen_US
dc.date.issued2022en_US
dc.description.abstractDespite 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.en_US
dc.identifier.citationGriffith, Brian D., Turcotte, Simon, Lazarus, Jenny, et al.. "MHC Class II Expression Influences the Composition and Distribution of Immune Cells in the Metastatic Colorectal Cancer Microenvironment." <i>Cancers,</i> 14, no. 17 (2022) MDPI: https://doi.org/10.3390/cancers14174092.en_US
dc.identifier.digitalcancers-14-04092en_US
dc.identifier.doihttps://doi.org/10.3390/cancers14174092en_US
dc.identifier.urihttps://hdl.handle.net/1911/113771en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleMHC Class II Expression Influences the Composition and Distribution of Immune Cells in the Metastatic Colorectal Cancer Microenvironmenten_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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