Considering that ISG15 can be secreted extracellularly and the amount of ISG15 exocytosis increases with its basal expression (Fig. 3E), We hypothesized that increased ISG15 secretion might contribute to the differentiation and proliferation of Th1-type CD4+ T lymphocytes, thus enabling them to kill more target tumor cells. This evidence concerns the gene ISG15 and neoplasm.