PMID- 12445285 OWN - NLM STAT- MEDLINE DCOM- 20030616 LR - 20201222 IS - 0105-2896 (Print) IS - 0105-2896 (Linking) VI - 188 DP - 2002 Oct TI - Antitumor cytotoxic T-lymphocyte response in human lung carcinoma: identification of a tumor-associated antigen. PG - 114-21 AB - We have isolated several cytotoxic T lymphocyte (CTL) clones from lymphocytes infiltrating a lung carcinoma of a patient with long survival. These clones showed a CD3+, CD8+, CD4-, CD28- phenotype and expressed a T-cell receptor (TCR) encoded either by Vbeta8-Jbeta1.5 or Vbeta22-Jbeta1.4 rearrangements. Functional studies indicated that these clones mediated a high human leukocyte antigen (HLA)-A2.1-restricted cytotoxic activity against the autologous tumor cell line. Interestingly, TCRbeta chain gene usage indicated that CTL clones identified in vitro were selectively expanded in vivo at the tumor site as compared to autologous peripheral blood lymphocytes (PBL). These findings provide evidence that an immune response may take place in non-small cell lung carcinoma and that effector T cells may contribute to tumor regression. Further study indicated that the CTL clones recognized the same decamer peptide encoded by a mutated alpha-actinin-4 gene. Using tetramers of soluble HLA-A2 molecules loaded with the mutated antigenic peptide, we have derived several anti-alpha-actinin-4 T-cell clones from patient PBL. These CTL, recognizing a truly tumor-specific antigen, may play a role in the clinical evolution of this lung cancer patient. Adoptive transfer of CTL clones in a SCID/NOD mice model transplanted with autologous tumor supported their antitumor effect in vivo. FAU - Mami-Chouaib, Fathia AU - Mami-Chouaib F AD - Laboratoire Cytokines et Immunologie des tumeurs Humaines, U487 INSERM, Institut Federatif de Recherche-54, Institut Gustave Roussy, Villejuif, France. cfathia@igr.fr FAU - Echchakir, Hamid AU - Echchakir H FAU - Dorothee, Guillaume AU - Dorothee G FAU - Vergnon, Isabelle AU - Vergnon I FAU - Chouaib, Salem AU - Chouaib S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Immunol Rev JT - Immunological reviews JID - 7702118 RN - 0 (ACTN4 protein, human) RN - 0 (Actn4 protein, mouse) RN - 0 (Antigens, Neoplasm) RN - 0 (HLA-A2 Antigen) RN - 0 (Microfilament Proteins) RN - 0 (Neoplasm Proteins) RN - 11003-00-2 (Actinin) SB - IM MH - Actinin/chemistry/*immunology MH - Amino Acid Sequence MH - Animals MH - Antigen Presentation MH - Antigens, Neoplasm/*immunology MH - Carcinoma, Non-Small-Cell Lung/*immunology/pathology MH - Clone Cells/immunology MH - Cytotoxicity, Immunologic MH - Gene Rearrangement, beta-Chain T-Cell Antigen Receptor MH - HLA-A2 Antigen/immunology MH - Humans MH - Immunophenotyping MH - Immunotherapy, Adoptive MH - Lung Neoplasms/*immunology/pathology MH - Lymphocytes, Tumor-Infiltrating/*immunology MH - Mice MH - Mice, Inbred NOD MH - Mice, SCID MH - *Microfilament Proteins MH - Molecular Sequence Data MH - Neoplasm Proteins/chemistry/*immunology MH - T-Lymphocytes, Cytotoxic/*immunology MH - T-Lymphocytes, Regulatory/immunology MH - Tumor Cells, Cultured/immunology MH - Xenograft Model Antitumor Assays RF - 51 EDAT- 2002/11/26 04:00 MHDA- 2003/06/17 05:00 CRDT- 2002/11/26 04:00 PHST- 2002/11/26 04:00 [pubmed] PHST- 2003/06/17 05:00 [medline] PHST- 2002/11/26 04:00 [entrez] AID - imr18810 [pii] AID - 10.1034/j.1600-065x.2002.18810.x [doi] PST - ppublish SO - Immunol Rev. 2002 Oct;188:114-21. doi: 10.1034/j.1600-065x.2002.18810.x.