[Analysis of growth, phenotype and cytotoxic activity of tumor infiltrating lymphocytes expanded in vitro with interleukin-2 and interleukin-4: preliminary results]. / Analisi della crescita, del fenotipo e dell'attività citotossica dei linfociti infiltranti i tumori espansi in vitro con interleuchina 2 ed interleuchina 4: risultati preliminari.

ABSTRACT

Tumor infiltrating lymphocytes (TIL) play an important role in the host immune response to cancer. When these cells are reinfused into cancer patients after in vitro expansion with lymphokines such as interleukin 2 (rIL-2), they often induce regression of tumor metastases. We obtained TIL of enzymatic digestion of 7 human solid tumors and then cultured them with rIL-2 and interleukin 4 (IL-4) at different concentrations for about 36 days. Immunophenotypic analysis was performed at the end of the second and fourth week; cytotoxic activity against autologous and heterologous targets was assessed on the 30th day of culture. The best lymphocytic growth was observed when we used rIL-2 and IL-4 for the first two weeks of culturing and then continued with rIL-2 alone. CD3 and CD56 cells formed the majority of TIL in all cultures. In 4 cases CD4 cells predominated at the initial stage of culturing, with CD8 cells gradually increasing and finally inverting the CD4/CD8 ratio. Autologous cytotoxicity (3/4 cases) appeared to be better in those patients in whom the CD4/CD8 ratio was inverted. These data enable identification of the combination of lymphokines that will will best provide expansion of live TIL active against tumoral cells. This procedure must be followed before in vivo reinfusion of expanded lymphocytes is carried out.