ISOLATION AND CHARACTERIZATION OF TUMOR-INFILTRATING LYMPHOCYTES FROMCERVICAL-CARCINOMA

The evidence that virus-induced tumors generally elicit T-cell respons es prompts the notion that HPV-related cervical carcinoma would be ame nable to treatment by T-cell-mediated adoptive therapy. Therefore, we cultured and cloned tumor-infiltrating lymphocytes (TIL) from a patien t with cervical carcinoma and studied the in vitro characteristics of these TIL by using the established autologous tumor-cell line. After s timulation of bulk TIL cultures with 1,000 Units/ml recombinant interl eukin 2 (rIL-2), followed by limiting dilution, T-cell clones were gen erated in the presence of 20 U/ml rIL-2 and irradiated autologous tumo r cells, PBLs and EBV-transformed B-cell lines. Phenotypically, all cl ones were CD3/CD8-positive with a heterogeneous CD56 expression. All e xpressed preferential cytolytic activity against autologous tumor cell s, did not lyse autologous lymphoblasts, and were cytotoxic against th e NK-sensitive cell line K562. A minor lytic capacity was detectable o n allogeneic cervical tumor-cell lines or tumor-cell lines of other hi stologic types. Cytotoxicity against the autologous tumor could by ant i-HLA class-I (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 s urface antigen recognition is involved. These results may prove useful in further studies on adoptive immunotherapy of cervical cancer patie nts. (C) 1994 Wiley-Liss, Inc.