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

• Main Authors: Cai, L. (Author), Durrant, L.G (Author), Ferrone, S. (Author), Kontos, F. (Author), Krijgsman, D. (Author), Kuppen, P.J.K (Author), Kurokawa, T. (Author), Michelakos, T. (Author), R Ferrone, C. (Author), Sadagopan, A. (Author), Weichert, W. (Author)
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2022
• Subjects: adaptive immunity; gastrointestinal neoplasms; receptors, immunologic; T-lymphocytes
• Online Access: View Fulltext in Publisher

 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. © 2022 BMJ Publishing Group. All rights reserved.