The immunosuppression of tumor-infiltrating lymphocytes (TILs) is associated with rapid progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). T cell Ig- and mucin-domain-containing molecule-3 (Tim-3) and programmed cell death 1 (PD-1) are important inhibitory molecules expressed on the surface of T cells, but their roles in the function of TILs in HBV-HCC are poorly understood. We aimed to study the roles of these two markers in HBV-HCC.
Ninety patients with pathologically confirmed HBV-associated HCC were enrolled in our study. Blood samples, paired fresh tumor tissues and adjacent tissues were collected, and isolating peripheral blood mononuclear cells, TILs and adjacent-infiltrating lymphocytes were isolated from these samples. The patients were followed-up to allow survival analysis.
Tim-3 or/and PD-1 was up-regulated expressed on CD4+ and CD8+ TILs in HBV-HCC patients and a higher proportion of TILs expressed PD-1 alone. Tim-3+ and PD-1+ TILs greatly decreased secretion of IFN-? and TNF-a. Expression of Tim-3 and PD-1 on TILs negatively correlated with disease-free survival of HCC patients. Direct blockade of Tim-3 and PD-1 in vitro significantly enhanced TILs proliferation and secretion of IFN-? and TNF-a.
Expression of Tim-3 and/or PD-1 on TILs impairs their function and correlates negatively with disease-free survival in HBV-HCC. Direct blockade of Tim-3 and PD-1 restores anti-tumor effects of TILs, which suggests a potential target for novel immunotherapy in HBV-HCC.Le texte complet de cet article est disponible en PDF.
Mots clés : TIM3, Protéine PD-1, TILs, HBV, Carcinome hépatocellulaire
Keywords : TIM3 (T cell Ig- and mucin-domain-containing molecule-3), PD-1 (Programmed cell death 1), TILs, HBV: hepatocellular carcinoma
Vol 105 - N° 5P. 493-501 - mai 2018 Retour au numéro
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