title: HLA-E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression.
abstract: The host immune response plays a major role in colorectal carcinoma (CRC) progression. A mechanism of tumor immune escape might involve expression of the human leucocyte antigen (HLA)-E/β2m on tumor cells. The inhibitory effect of HLA-E/β2m on CD8+ cytotoxic T lymphocytes and natural killer (NK) cells is mediated by the main HLA-E receptor CD94/NKG2A. As the pathophysiological relevance of this mechanism in CRC remains unknown, this prompted us to examine, in situ, in a series of 80 CRC (i) the HLA-E and β2m coexpression by tumor cells, (ii) the density of CD8+, cytotoxic, CD244+ and NKP46+ intraepithelial tumor-infiltrating lymphocyte (IEL-TIL) and (iii) the expression of CD94/NKG2 receptor on IEL-TIL. These data were then correlated to patient survival. We provided (i) the in situ demonstration of HLA-E/β2m overexpression by tumor cells in 21% of CRC characterized by an overrepresentation of signet ring cell carcinomas, mucinous carcinomas and medullary carcinomas, (ii) the significant association between HLA-E/β2m overexpression by tumor cells and increased density of CD8+ cytotoxic, CD244+ and CD94+ IEL-TIL and (iii) finally, the unfavorable prognosis associated with HLA-E/β2m overexpression by tumor cells. Our findings show that HLA-E/β2m overexpression is a surrogate marker of poor prognosis and point to a novel mechanism of tumor immune escape in CRC in restraining inhibitory IEL-TIL.
authors.affiliation: INSERM U892, F-44093 Nantes, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Bossard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
authors.forename: Tamara
authors.initials: T
authors.lastname: Matysiak-Budnik
authors.forename: Christelle
authors.initials: C
authors.lastname: Volteau
authors.forename: Christian L
authors.initials: CL
authors.lastname: Laboisse
authors.forename: Francine
authors.initials: F
authors.lastname: Jotereau
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mosnier
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008297:Male; D011379:Prognosis; D016019:Survival Analysis; D046888:Tissue Array Analysis; D019139:Tumor Escape; D001613:beta 2-Microglobulin / Q000378:metabolism*; D000097625:HLA-E Antigens
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin; D000097625:HLA-E Antigens