MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating urothelial carcinomas

Franck Housseau, Dominique Zeliszewski, Maguy Roy, Valerie Paradis, Sophie Richon, Alice Rigour, Joelle Bougaran, Dominique Prapotnich, Guy Vallancien, Gérard Benoit, Laurent Desportes, Pierre Bedossa, Thierry Hercend, Jean Michel Bidart, Dominique Bellet

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell lines established from these urothelial tumors were used as target cells in cytolysis assays in order to investigate the functional anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL lines displayed MHC-class-I-dependent cytotoxicity directed against autologous tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed that CD8+ MHC-class-I-dependent CTL were the predominant effecters. Finally, experiments performed on 6 allogeneic urothelial cancer cell lines matched for HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in urothelial carcinomas are functional and may participate in the anti-tumor immune response.

Original languageEnglish (US)
Pages (from-to)585-594
Number of pages10
JournalInternational Journal of Cancer
Volume71
Issue number4
DOIs
StatePublished - Jun 19 1997
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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