PMID- 16077989 OWN - NLM STAT- MEDLINE DCOM- 20050915 LR - 20181201 IS - 1021-335X (Print) IS - 1021-335X (Linking) VI - 14 IP - 3 DP - 2005 Sep TI - Generation of diverse mutated tumor antigen-specific cytotoxic T lymphocytes in a lung cancer patient with long survival. PG - 763-9 AB - We have identified an antigen recognized on a large cell carcinoma of the lung by tumor-specific cytotoxic T lymphocytes (CTL). The antigenic peptide is encoded by a mutated alpha-actinin-4 gene and presented by human leukocyte antigen (HLA)-A2. Using HLA-A2-peptide tetramers, we have derived from patient peripheral blood lymphocytes (PBL) and autologous tumor infiltrating lymphocytes (TIL) several mutated alpha-actinin-4-specific T cell clones. These clones displayed similar tetramer staining but distinct T cell receptor (TCR) usage and antitumor reactivity. Indeed, TIL clones lysed more efficiently the autologous tumor cells and released higher cytokine levels than PBL clones. Importantly, treatment of cancer cells with interferon-gamma enhanced their susceptibility to PBL clone-mediated lysis correlated with increase in HLA-class I expression. The present findings provide evidence that an immune T cell response took place in a lung cancer patient with favorable clinical evolution and suggest that CTL, recognizing a truly tumor-specific antigen, may contribute to controlling the tumor. FAU - El Hage, Faten AU - El Hage F AD - Laboratoire Cytokines et Immunologie des Tumeurs Humaines, U487 INSERM, Institut Federatif de Recherche-54, F-94 805 Villejuif, France. FAU - Vergnon, Isabelle AU - Vergnon I FAU - Grunenwald, Dominique AU - Grunenwald D FAU - Soria, Jean Charles AU - Soria JC FAU - Chouaib, Salem AU - Chouaib S FAU - Mami-Chouaib, Fathia AU - Mami-Chouaib F LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Cytokines) RN - 0 (HLA-A2 Antigen) RN - 0 (Microfilament Proteins) RN - 11003-00-2 (Actinin) SB - IM MH - Actinin/*genetics/immunology MH - Aged MH - Carcinoma, Large Cell/genetics/immunology/*pathology MH - Cytokines/metabolism MH - Cytotoxicity Tests, Immunologic MH - Cytotoxicity, Immunologic/immunology MH - Flow Cytometry MH - Follow-Up Studies MH - HLA-A2 Antigen/immunology MH - Humans MH - Lung Neoplasms/genetics/immunology/*pathology MH - Male MH - Microfilament Proteins/*genetics/immunology MH - Mutation MH - T-Lymphocytes, Cytotoxic/*immunology/metabolism/pathology EDAT- 2005/08/04 09:00 MHDA- 2005/09/16 09:00 CRDT- 2005/08/04 09:00 PHST- 2005/08/04 09:00 [pubmed] PHST- 2005/09/16 09:00 [medline] PHST- 2005/08/04 09:00 [entrez] PST - ppublish SO - Oncol Rep. 2005 Sep;14(3):763-9.