Isolation and characterization of tumor-infiltrating lymphocytes from cervical carcinoma

Int J Cancer. 1994 Jun 15;57(6):805-13. doi: 10.1002/ijc.2910570608.

Abstract

The evidence that virus-induced tumors generally elicit T-cell responses prompts the notion that HPV-related cervical carcinoma would be amenable to treatment by T-cell-mediated adoptive therapy. Therefore, we cultured and cloned tumor-infiltrating lymphocytes (TIL) from a patient with cervical carcinoma and studied the in vitro characteristics of these TIL by using the established autologous tumor-cell line. After stimulation of bulk TIL cultures with 1,000 Units/ml recombinant interleukin 2 (rIL-2), followed by limiting dilution, T-cell clones were generated in the presence of 20 U/ml rIL-2 and irradiated autologous tumor cells, PBLs and EBV-transformed B-cell lines. Phenotypically, all clones were CD3/CD8-positive with a heterogeneous CD56 expression. All expressed preferential cytolytic activity against autologous tumor cells, did not lyse autologous lymphoblasts, and were cytotoxic against the NK-sensitive cell line K562. A minor lytic capacity was detectable on allogeneic cervical tumor-cell lines or tumor-cell lines of other histologic types. Cytotoxicity against the autologous tumor could be inhibited by anti-CD3, anti-CD8 and anti-ICAM1 but not by anti-HLA class-1 (W6/32, B9.12.1), anti-allele-specific HLA determinants and anti-LFA-3 antibodies. We demonstrate a highly specific autologous lytic activity of cervical carcinoma TIL, in which a CD3-associated surface antigen recognition is involved. These results may prove useful in further studies on adoptive immunotherapy of cervical cancer patients.

MeSH terms

  • Adult
  • Carcinoma / immunology*
  • Cell Separation
  • Clone Cells
  • Cytotoxicity, Immunologic
  • Female
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Humans
  • Immunophenotyping
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Uterine Cervical Neoplasms / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta