Intraepithelial CD94+ tumor-infiltrating lymphocytes in a context of HLA-E overexpression as a new immune checkpoint to predict prognosis in colorectal carcinomas.

• DOI: 10.1200/jco.2017.35.15_suppl.e14592
• Publication Date: 2018-09-06T15:42:53Z
• Authors: Celine Bossard; Juliette Eugene; Nicolas Jouand; Delphine Dansette; Edouard Leveque; Juliette Podevin; Tamara Matysiak; Stephane Bezieau; Jerome Chetritt; Olivier Kerdraon; Pierre Fourquier; Emilie Thibaudeau; Jean-François Mos...; Anne Jarry; Nadine Gervois
• Keywords: Intraepithelial lymphocyte; Tumor-infiltrating lymphocytes; Microsatellite Instability; HLA-G

e14592 Background: A better understanding of the immune-modulating interactions between tumor cells and immune underlying balance control resistance in colorectal cancer (CRC) is crucial for design immunotherapies. We have previously demonstrated that overexpression human MHC class Ib molecule - HLA-E/β2 microglobulin by CRC was associated with an unfavorable prognosis, suggesting its involvement escape. However, specific receptor HLA-E/β2m CD94/NKG2A, inhibitory or CD94/NKG2C, activating expressed tumor-infiltrating lymphocytes (TIL), as well influence microsatellite status overexpression, remain unknown. Methods: investigated primary 245 patients 1) association density CD94 + intraepithelial TIL (IEL-TIL) status, 2) nature CD94/NKG2A CD94/NKG2C 3) prognostic IEL-TIL. Results: preferentially overexpressed MSI compared MSS (44,6 % vs 18,4 respectively, p = 0.0001), significantly a high IEL-TIL (0,9% 0,2% – CRC, 0,001), (0,38% 0,15%, < 0,0001). These mostly corresponded to CD8 αβ T expressing NKG2A chain. Finally, independently worse OS (p 0.03). Conclusions: results strongly suggest interactions, up-regulated represent promising checkpoint. From clinical point view, this checkpoint could be blocked new anti-NKG2A monoclonal antibody.