Although CD4+ T cells might play a role in the anti-tumor response elicited by Lm-LLO-ISG15, as demonstrated by an increased influx of CD4+ T-cells in the TME, we found that the therapeutic efficacy of Lm-LLO-ISG15 is mainly mediated by the CD8+ T-cell. The gene discussed is ISG15; the disease is neoplasm.