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World J Gastroenterol. Apr 14, 2014; 20(14): 3778-3794
Published online Apr 14, 2014. doi: 10.3748/wjg.v20.i14.3778
Inhibition of host immune response in colorectal cancer: Human leukocyte antigen-G and beyond
Marica Garziera, Giuseppe Toffoli
Marica Garziera, Giuseppe Toffoli, Experimental and Clinical Pharmacology Unit, CRO Aviano National Cancer Institute, 33081 Aviano, Italy
Author contributions: Garziera M and Toffoli G established the design and conception of the paper; Garziera M analyzed the literature data and provided the first draft of the manuscript; Garziera M created figures and tables; Toffoli G discussed and revised critically for intellectual content; Garziera M submitted the manuscript; and Toffoli G approved the final version prior to publication.
Supported by Associazione Italiana per la Ricerca sul Cancro (AIRC), Special Program Molecular Clinical Oncology, 5X1000, No. 12214 (G.T.); European Research Council, Programme ‘‘Ideas’’, Proposal No. 269051 (G.T., F.R.)
Correspondence to: Marica Garziera, PhD, Experimental and Clinical Pharmacology Unit, CRO Aviano National Cancer Institute, via Franco Gallini 2, 33081 Aviano, Italy. mgarziera@cro.it
Telephone: +39-434-659816 Fax: +39-434-659799
Received: October 25, 2013
Revised: January 22, 2014
Accepted: February 26, 2014
Published online: April 14, 2014
Abstract

Colorectal cancer (CRC) is one of the most diffuse cancers worldwide and is still a clinical burden. Increasing evidences associate CRC clinical outcome to immune contexture represented by adaptive immune cells. Their type, density and location are summarized in the Immune Score that has been shown to improve prognostic prediction of CRC patients. The non-classical MHC class I human leukocyte antigen-G (HLA-G), is a crucial tumor-driven immune escape molecule involved in immune tolerance. HLA-G and soluble counterparts are able to exert inhibitory functions by direct interactions with inhibitory receptors present on both innate cells such as natural killer cells, and adaptive immune cells as cytotoxic T and B lymphocytes. HLA-G may play a prominent role in CRC strategies to avoid host immunosurveillance. This review highlights the current knowledge on HLA-G contribution in CRC, in related inflammatory diseases and in other type of cancers and disorders. HLA-G genetic setting (specific haplotypes, genotypes and alleles frequencies) and association with circulating/soluble profiles was highlighted. HLA G prognostic and predictive value in CRC was investigated in order to define a novel prognostic immune biomarker in CRC.

Keywords: Colorectal cancer, Human leukocyte antigen-G, Immune score, T lymphocytes, Untranslated regions

Core tip: Colorectal cancer (CRC) prognosis is strictly associated with the immune contexture of tumor microenvironment. IS improves prognostic prediction in CRC. Human leukocyte antigen-G (HLA-G) through its direct inhibitory functions on NK cells and cytotoxic T and B lymphocytes represents a crucial tumor-driven immune escape molecule. This review highlights the current knowledge on HLA-G in CRC and in related inflammatory diseases. HLA-G genetic setting and circulating/soluble profiles need to be defined to comprehend CRC strategies to avoid host immune defences. We suggest that HLA G could represent a novel prognostic immune biomarker to associate with the Immune Score to better characterize host immune response in CRC.