Human melanoma-mediated inhibition of autologous CD4+ helper tumor-infiltrating lymphocyte growth in vitro.
Tumor-infiltrating lymphocytes (TIL) were isolated from a human melanoma metastatic to the abdomen. The TIL were 99% CD3+ and 99% CD4+ and CD8-. They were dependent on interleukin-2 (IL-2) for growth, as measured in a thymidine uptake assay, and were not cytotoxic to autologous or allogeneic melanoma or K562. When co-cultured with irradiated autologous tumor cells, or tumor cell supernatants, the TIL not only did not respond, but the IL-2-dependent growth was inhibited significantly. Inhibition occurred during the first 24 hours of co-culture and persisted as long as the tumor was present. After being washed free of inhibitory tumor cells, the TIL again were able to grow in the presence of IL-2, indicating that the inhibition was not caused by irreversible toxicity mediated by the tumor. Addition of excess IL-2 did not reverse the inhibitory effect, but addition of indomethacin, an inhibitor of cyclooxygenase and prostaglandin synthesis, partially blocked the inhibition. These data show melanoma-mediated inhibition of induction and expansion of human T-cells in vitro, which may reflect one of the mechanisms of inhibition of cellular responses in vivo. These results stress the need to examine the techniques for optimal in vitro expansion of tumor-specific TIL or cytotoxic T-cells for adoptive immunotherapy.
Darrow
T L
TL
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Wahab
Z
Z
Quinn-Allen
M A
MA
Seigler
H F
HF
D001685:Biological Factors / Q000494:pharmacology; D015704:CD4 Antigens / Q000032:analysis* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002457:Cell Extracts / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D011453:Prostaglandins / Q000096:biosynthesis / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D001685:Biological Factors; D015704:CD4 Antigens; D002457:Cell Extracts; D007376:Interleukin-2; D011453:Prostaglandins