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Titre : | Blocking Tim-3 or/and PD-1 reverses dysfunction of tumor-infiltrating lymphocytes in HBV-related hepatocellular carcinoma (2018) |
Auteurs : | Furong Liu ; Gucheng Zeng ; Anbin Hu ; et al. |
Type de document : | Article |
Dans : | Bulletin du cancer (Vol. 105, n° 5, Mai 2018) |
Article en page(s) : | p. 493-501 |
Note générale : | https://doi.org/10.1016/j.bulcan.2018.01.018 |
Langues: | Français |
Mots-clés: | Immunothérapie adoptive ; Carcinome hépatocellulaire ; Virus de l'hépatite B ; Lymphocytes TIL ; Récepteur-1 de mort cellulaire programmée ; Protéine HAVCR2, humain ; TIM3 ; T cell Ig- and mucin- domain-containing molecule-3 ; PD-1 ; HBV-HCC ; carcinome hépatocellulaire associé au virus de l'hépatite B |
Résumé : |
Background 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. Methods 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. Results 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. Conclusion 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. |
Disponible en ligne : | Non |
Exemplaires (1)
Cote | Support | Localisation | Section | Disponibilité |
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REV | Périodique papier | Woluwe | Espace revues | Consultation sur place uniquement Exclu du prêt |