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HLA‐E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression
Author(s) -
Bossard Céline,
Bézieau Stéphane,
MatysiakBudnik Tamara,
Volteau Christelle,
Laboisse Christian L.,
Jotereau Francine,
Mosnier JeanFrançois
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26453
Subject(s) - cytotoxic t cell , tumor infiltrating lymphocytes , immune system , cancer research , intraepithelial lymphocyte , human leukocyte antigen , cd8 , biology , colorectal cancer , immunology , antigen , cancer , in vitro , biochemistry , genetics
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.