Human tumor-infiltrating lymphocyte (TIL) cytotoxicity facilitated by anti-T-cell receptor antibody

✍ Scribed by Deric D. Schoof; Sung-Eun Jung; Timothy J. Eberlein

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: French
• Weight: 637 KB
• Volume: 44
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910440205

✦ Synopsis

Long

-term growth of tumor-infiltrating lymphocytes (TIL) in high concentrations of rlL-2 is required for generation of therapeutic numbers of cells for adoptive immunotherapy of human cancer. Under these conditions rlL-2 promotes both anti-tumor cytotoxicity and lymphocyte growth from tumors of several histological types. In a series of 16 consecutive tumors, studies of TlL-mediated cytotoxicity against different tumor targets were characterized by an initial strong tumornon-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 tar- gets. 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 2), (p < 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 shortterm 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.