Expansion of Tumor-Infiltrating Lymphocytes from Human Tumors Using the T-Cell Growth Factors Interleukin-2 and Interleukin-4

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Abstract
Summary: We examined the role of two T cell-growth factors, interleukin (IL)-2 and IL-4, in expansion of tumor-infiltrating lymphocytes (TILs) from human tumors. In sarcoma, IL-4 (1,000 U/ml) with IL-2 (10 or 1,000 U/ml) grew TILs better than did IL-2 alone in six of 10 cases during 6 weeks of culture. IL-4 decreased the relative number of CD56+ cells, which correlated with a decrease in cytolysis against Daudi in six of 10 cases. The addition of IL-4 with 1,000 U of IL-2 maintained or increased cytolysis against autologous sarcoma, while decreasing nonspecific cytolysis against Daudi or allogeneic sarcoma in three of eight cases. IL-4 decreased cytolysis against both autologous sarcoma and Daudi in four of 10 cases, suggesting nonspecific activity in these instances. In renal cell cancer (RCC), IL-4 with IL-2 (10 or 1,000 U/ml) augmented TIL growth in six of eight cases, especially during the first 2-3 weeks of culture. IL-4 with 10 U of IL-2 increased cytolysis against both autologous RCC and Daudi in six of eight cases, suggesting possible prior cell activation. In contrast, IL-4 addition with 1,000 U of IL-2 maintained or increased cytolysis against autologous RCC, while decreasing cytolysis against Daudi or allogeneic RCC in four of eight cases. In cases of bladder and of prostate cancer, IL-4 with 1,000 U of IL-2 grew TILs slightly better in five of seven cases for the first 2-3 weeks. Bladder TILs grown with IL-2 and/or IL-4 were CD+ T cell predominant (three of five) and rarely lytic for autologous tumor. In colon cancer and hepatoma, TILs grown with IL-2 and/or IL-4 were nonlytic for the autologous tumor. IL-4 in conjunction with IL-2 could therefore augment growth of some TILs especially for the first 2-3 weeks from various human tumors.

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