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

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dc.citation.articleNumber4092
dc.citation.issueNumber17
dc.citation.journalTitleCancers
dc.citation.volumeNumber14
dc.contributor.authorGriffith, Brian D.
dc.contributor.authorTurcotte, Simon
dc.contributor.authorLazarus, Jenny
dc.contributor.authorLima, Fatima
dc.contributor.authorBell, Samantha
dc.contributor.authorDelrosario, Lawrence
dc.contributor.authorMcGue, Jake
dc.contributor.authorKrishnan, Santhoshi
dc.contributor.authorOneka, Morgan D.
dc.contributor.authorNathan, Hari
dc.contributor.authorSmith, J. Joshua
dc.contributor.authorD’Angelica, Michael I.
dc.contributor.authorShia, Jinru
dc.contributor.authorDi Magliano, Marina Pasca
dc.contributor.authorRao, Arvind
dc.contributor.authorFrankel, Timothy L.
dc.date.accessioned2022-10-28T17:43:08Z
dc.date.available2022-10-28T17:43:08Z
dc.date.issued2022
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.
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.
dc.identifier.digitalcancers-14-04092
dc.identifier.doihttps://doi.org/10.3390/cancers14174092
dc.identifier.urihttps://hdl.handle.net/1911/113771
dc.language.isoeng
dc.publisherMDPI
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleMHC Class II Expression Influences the Composition and Distribution of Immune Cells in the Metastatic Colorectal Cancer Microenvironment
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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