Selective lysis of autologous tumor cells by recurrent gamma delta tumor-infiltrating lymphocytes from renal carcinoma.
We show here that tumor infiltrating lymphocytes (TIL) derived from three renal carcinoma (RC) tumors, which developed in the same patient over a 3-yr period, were systematically enriched in gamma delta + T cells (27-74%) after short term in vitro culture. Analysis of the repertoire of gamma delta + TIL and PBL from this patient, revealed the predominant expression of structurally diverse V delta 1 gamma delta TCR by TIL from the three tumors, contrasting with the classically dominant use of V delta 2 TCR by PBL. Functional analysis further showed that, independently of the V gamma genes expressed, all the V delta 1+ TIL clones exhibited a lytic activity apparently restricted to RC lines, while V gamma 9+V delta 2+ clones (either PBL- or TIL-derived) had a broad killing activity. Surprisingly most V delta 1+ CTL clones lysed several allogeneic, but not the autologous, RC lines. Only one V gamma 3+V delta 1+ TIL clone, identified by its specific variable TCR gene sequence, consistently killed autologous tumor cells, apparently via TCR-mediated MHC-unrestricted recognition. This clone also lysed two allogeneic RC lines out of four tested but did not kill 30 non-RC lines, except for one breast carcinoma line. Significantly, this clone was found in recurrent fashion in all three tumors analyzed, including a metastasis. The high frequency of V delta 1 expressing RC-reactive gamma delta cells among TIL from this patient suggests that this gamma delta subset was selectively trapped and/or preferentially induced to proliferate in the autologous tumors. The recurrence of a single V gamma 3+V delta 1+ gamma delta clone, reacting with autologous tumor cells, inside three tumors of different localizations additionally suggests that, for this clone, intratumor selection and/or proliferation was due to TCR-mediated recognition of a non-MHC-restricted RC-specific Ag.
Choudhary
A
A
INSERM Unit 211, Institute of Biology, Nantes, France.
Davodeau
F
F
Moreau
A
A
Peyrat
M A
MA
Bonneville
M
M
Jotereau
F
F
D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000737:chemistry; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007680:Kidney Neoplasms / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D017931:DNA Primers; D016692:Receptors, Antigen, T-Cell, gamma-delta