{"doi":"10.3390/cancers14174092","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.","journal":"Cancers","year":2022,"id":261232,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9616,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562940,"name":"Simon Turcotte","orcid":"0000-0002-9003-812X","position":1,"is_corresponding":false},{"id":225398,"name":"Jenny Lazarus","orcid":"0000-0002-9001-1453","position":2,"is_corresponding":false},{"id":915503,"name":"Fátima Lima","orcid":"0000-0002-5025-6958","position":3,"is_corresponding":false},{"id":225401,"name":"Samantha L. Bell","orcid":"0000-0002-5453-3203","position":4,"is_corresponding":false},{"id":225397,"name":"Lawrence Delrosario","orcid":"0000-0002-0863-8936","position":5,"is_corresponding":false},{"id":915504,"name":"Jake McGue","orcid":"0000-0001-6131-7798","position":6,"is_corresponding":false},{"id":881088,"name":"Santhoshi Krishnan","orcid":"0000-0001-5114-9778","position":7,"is_corresponding":false},{"id":262532,"name":"Morgan Oneka","orcid":"0000-0002-9672-0445","position":8,"is_corresponding":false},{"id":225415,"name":"Hari Nathan","orcid":"0000-0001-7402-2403","position":9,"is_corresponding":false},{"id":239559,"name":"J. Joshua Smith","orcid":"0000-0003-2538-5456","position":10,"is_corresponding":false},{"id":303268,"name":"Michael I. D’Angelica","orcid":null,"position":11,"is_corresponding":false},{"id":239557,"name":"Jinru Shia","orcid":"0000-0002-4351-2511","position":12,"is_corresponding":false},{"id":225422,"name":"Marina Pasca di Magliano","orcid":"0000-0001-9632-9035","position":13,"is_corresponding":false},{"id":69715,"name":"Arvind Rao","orcid":"0000-0002-9613-426X","position":14,"is_corresponding":false},{"id":225421,"name":"Timothy L. Frankel","orcid":"0000-0001-5987-0404","position":15,"is_corresponding":false},{"id":915502,"name":"Brian D. Griffith","orcid":"0000-0001-6580-7217","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T00:26:12.158801Z","pmid":"36077630","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}