Isolation and characterization of tumor-infiltrating lymphocytes from cervical carcinoma

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 tumorinfiltrating 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‐ICAMI but not by anti‐HLA class‐1 (W6/32, B9.12.I), 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. © 1994 Wiley‐Liss, Inc.