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Differential role of HLA-A and HLA-B, C expression levels as prognostic markers in colon and rectal cancer

Year: 2022
Type: article
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.
DOI: 10.1136/jitc-2021-004115
Authors: Theodoros Michelakos, Filippos Kontos, Tomohiro Kurokawa, Lei Cai, Ananthan Sadagopan, Danielle Krijgsman, Wilko Weichert, Lindy G Durrant, Peter J K Kuppen, Cristina R Ferrone, Soldano Ferrone
Institutions: Harvard University, Massachusetts General Hospital, Utrecht University, Leiden University Medical Center, University Medical Center Utrecht, Technical University of Munich, University of Nottingham, Nottingham City Hospital
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,490
Funders: McGill University, Generalitat de Catalunya, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research
Awards: Potential role of brachyury in HLA class I antigen processing machinery component downregulation in chordoma cells, G2823094387, T cell plasticity, fusion proteins and CAR T cell-based immunotherapy of head and neck cancer, G3261693824, G3288897321, G3522231704, G5252489644, G5593011625, ROLE OF THE HLA ANTIGEN PRESENTING MACHINERY (APM) IN RESISTANCE TO PD-1 AXIS BLOCKADE IN NON-SMALL CELL LUNG CANCER, G709838047, Understanding and Overcoming Resistance to Cancer Immunotherapy Due to Defective Antigen Presentation, G8660019549
OpenAlex ID: W4221108353
FWCI: 4.577
Cites: 39
Cited by: 31
Related to: 10