Evidence for cytotoxic T lymphocyte response against human lung cancer: Reconstitution of antigenic epitope with peptide eluted from lung adenocarcinoma MHC class I

Background. Cancer-associated, major histocompatibility complex (MHC)-restr icted peptide antigens have been elucidated in human melanomas and ovarian, breast, and renal carcinomas; but relatively little is known about lung ca ncer antigens. Methods. To work toward delineation of lung cancer-associated antigens, we developed tumor infiltrating lymphocytes (TILs), peripheral blood mononucle ar cell-derived cytolytic T cell lines (CTL), autologous lung cancer cell l ines, and normal lung cell lines form 17 patients undergoing lung cancer re sections. The TILs and CTL lines were subsequently evaluated for markers of activation and specific lysis of autologous or allogenic lung cancer cell lines or both. Results. Freshly isolated TILs contained a more activated T cell population compared with the patients' peripheral blood T cell sas evidenced by an in creased expression of HLA-DR, CD25, and CD45RO. TILs isolated from 15 patie nts lysed allogenic lung cancer lines. TILs lysed autologous lung cancer bu t not autologous normal lung or Epstein-Barr virus transformed B cell lines (B-LCL) in 4 of 8 cases tested, suggesting tumor specificity. A CTL line ( RHPBL57.1) was generated from peripheral blood mononuclear cells of an HLA- A24(+) patient by simulation against an established HLA-A24(+) allogenic lu ng cancer cel line. RHPBL57.1 lysed the lung cancer cell line in an HLA-A24 -restricted manner. Moreover, PHPBL57.1 specifically lysed autologous B-LCL pulsed with peptides, eluted from MHC class I and isolated from the HLA-A2 4(+) lung cancer cell line. Conclusions. TILs isolated from patients with lung cancer are predominantly an activated population of T cells wit evidence of tumor and MHC class I-r estricted lysis. Furthermore, we provide evidence for a lung cancer-associa ted, MHC class I-bound peptide antigen(s) that reconstitutes the epitope re cognized by a lung cancer specific CD8(+) T cell line derived from a patien t with lung cancer.