Human tumor-infiltrating lymphocyte (TIL) cytotoxicity facilitated by anti-T-cell receptor antibody.
Long-term growth of tumor-infiltrating lymphocytes (TIL) in high concentrations of rIL-2 is required for generation of therapeutic numbers of cells for adoptive immunotherapy of human cancer. Under these conditions rIL-2 promotes both anti-tumor cytotoxicity and lymphocyte growth from tumors of several histological types. In a series of 16 consecutive tumors, studies of TIL-mediated cytotoxicity against different tumor targets were characterized by an initial strong tumor-non-specific cytotoxicity. With time, TIL bulk cultures became non-cytotoxic against all targets (median time = 38 days). Non-cytotoxic TIL bulk populations were capable of mediating strong cytotoxic responses if pre-treated with anti-T-cell antigen receptor antibody (TcR) before addition to targets. TIL populations were not, however, uniformly susceptible to anti-TcR-mediated cytotoxicity. Anti-TcR-mediated cytotoxicity was confined to CD8+ bulk populations (defined as populations with a CD4/CD8 ratio less than 1), with virtually no cytotoxicity observed in CD4+ populations (CD4/CD8 ratio greater than 2, (p less than 0.01). Both CD4 and CD8 populations expressed TcR antigen reactive with anti-TcR antibody. These results indicate that, despite poor in vitro anti-tumor cytotoxicity in short-term assays, CD8+ TIL are fully competent cytotoxic effector cells when subjected to strong activation signals via the TcR complex. In addition, these results imply that adoptively transferred CD4+ populations of TIL have in vivo biologic functions quite distinct from those of CD8+ populations and, further, that disparate clinical outcomes could reasonably be expected from the adoptive transfer of either population alone.
Schoof
D D
DD
Division of Surgical Oncology, Brigham and Women's Hospital, Boston, MA.
Jung
S E
SE
Eberlein
T J
TJ
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016827:CD8 Antigens; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007167:Immunotherapy; D008214:Lymphocytes / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell