{"doi":"10.1136/jitc-2021-004115","title":"Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer","abstract":"PURPOSE: The association of human leucocyte antigen (HLA) class I expression levels with the clinical course of many malignancies reflects their crucial role in the recognition and elimination of malignant cells by cognate T cells and NK cells. In colorectal cancer, results regarding this association are conflicting. The potential pathogenetic and therapeutic implications of this association prompted us to perform a large patient-level pooled analysis assessing the role of the expression level of HLA class I loci gene products in colon and rectal cancer. EXPERIMENTAL DESIGN: Included studies provided patient-level data on HLA class I expression levels determined by immunohistochemistry on surgical specimens. Expression levels of the HLA class I loci gene products (HLA-A, HLA-B/C) were correlated with common genetic events and survival. RESULTS: Data from 5 studies including 2863 patients were used. In the 1620 colon cancer patients, lower HLA-A, HLA-B/C and total HLA class I expression levels were associated with microsatellite instability (p=0.044, p=0.008 and p=0.022, respectively), higher frequency of BRAF mutations (p<0.001, p=0.021 and p<0.001, respectively) and lower frequency of KRAS mutations (p=0.001, ns and p=0.002, respectively). In the 1243 rectal cancer patients, HLA-A expression was higher in tumors treated with neoadjuvant radiation (p=0.024). High HLA-B/C, but not HLA-A, expression level was an independent predictor of favorable overall survival in colon (p=0.006) and rectal (p<0.001) cancer. CONCLUSIONS: T-cells and HLA-B/C antigens, rather than NK cells and HLA-A antigens, likely play an important role in controlling colon/rectal cancer growth. Colon/rectal cancer patients may benefit from strategies that upregulate HLA-B/C and trigger or enhance T cell immunity.","journal":"Journal for ImmunoTherapy of Cancer","year":2022,"id":248843,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"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":345138,"name":"Filippos Kontos","orcid":"0000-0002-7011-4017","position":1,"is_corresponding":false},{"id":888425,"name":"Tomohiro Kurokawa","orcid":"0000-0002-7932-8724","position":2,"is_corresponding":false},{"id":888426,"name":"Lei Cai","orcid":"0000-0002-3489-4386","position":3,"is_corresponding":false},{"id":656964,"name":"Ananthan Sadagopan","orcid":"0000-0001-6306-4907","position":4,"is_corresponding":false},{"id":888427,"name":"Daniëlle Krijgsman","orcid":"0000-0001-6101-7146","position":5,"is_corresponding":false},{"id":65648,"name":"Wilko Weichert","orcid":"0000-0001-6139-8372","position":6,"is_corresponding":false},{"id":888428,"name":"Lindy G. Durrant","orcid":"0000-0002-7217-3707","position":7,"is_corresponding":false},{"id":15032,"name":"Peter J.K. Kuppen","orcid":"0000-0002-0294-3251","position":8,"is_corresponding":false},{"id":15997,"name":"Cristina R. Ferrone","orcid":"0000-0002-6295-1085","position":9,"is_corresponding":false},{"id":247569,"name":"Soldano Ferrone","orcid":"0000-0003-2900-8834","position":10,"is_corresponding":false},{"id":345137,"name":"Theodoros Michelakos","orcid":"0000-0002-4047-0926","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:14.794521Z","pmid":"35277460","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":[]}