HLA‐E/β2 microglobulin overexpression in colorectal cancer is associated with recruitment of inhibitory immune cells and tumor progression

International Journal of Cancer - Tập 131 Số 4 - Trang 855-863 - 2012
Céline Bossard1, Stéphane Bézieau2, Tamara Matysiak‐Budnik3, Christelle Volteau4, Christian Laboisse2, Francine Jotereau1, Jean‐François Mosnier5,2
1INSERM U892, F-44093 Nantes, France
2Université de Nantes, Faculté de Médecine de Nantes, EA 4273 Biometadys, 44035 Nantes, France
3Institut des Maladies de l'Appareil Digestif et Service d'Hépato-gastroentérologie, CHU de Nantes, France
4Plateforme de Biométrie, CHU de Nantes, France
5Tel.: 33-2-40-41-28-30,

Tóm tắt

AbstractThe 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.

Từ khóa


Tài liệu tham khảo

Naito Y, 1998, CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer, Cancer Res, 58, 3491

10.1056/NEJMoa051424

10.1126/science.1129139

10.1200/JCO.2008.19.6147

10.1038/86297

10.4049/jimmunol.0801878

10.1172/JCI36022

10.1016/S0167-5699(97)01115-8

10.1038/onc.2010.437

10.4049/jimmunol.177.5.3100

10.1038/35869

10.1093/jnen/64.6.523

Levy EM, 2008, Human leukocyte antigen E protein is overexpressed in primary human colorectal cancer, Int J Oncol, 32, 633

10.1073/pnas.95.9.5199

10.1385/IR:35:3:263

10.1007/978-3-642-58537-1_7

10.4049/jimmunol.177.6.3590

10.1016/j.smim.2006.03.002

10.1002/jso.21237

Hamilton SR, 2010, WHO classification of tumours of the digestive system, 134

10.1016/j.ygyno.2005.07.030

10.1111/j.1365-2567.2007.02660.x

10.1016/j.imbio.2010.09.012

10.1016/j.molimm.2004.07.032

10.1002/hep.23936

10.4049/jimmunol.178.2.652

10.1093/emboj/18.15.4250

10.1073/pnas.1834449100

10.4049/jimmunol.173.9.5852

10.1084/jem.190.6.775

10.1172/JCI43522

10.1158/0008-5472.CAN-04-2108

10.1016/j.ejca.2010.09.001

10.1016/S0002-9440(10)61695-1

10.1038/sj.bjc.6602201

10.1073/pnas.1100354108

Thông tin
Thông tin xuất bản

International Journal of Cancer

Tập 131 Số 4

855-863

Thông tin tác giả