There is evidence that cell-associated IL-1a supports immune response induction. Here we explored the impact of malignant cell-derived IL-1 on immunogenicity, immune response induction and tumor-induced immunosuppression using 3-methylcholanthrene-induced fibrosarcoma lines derived from wild-type (wt), IL-1a-, IL-1b-or IL-1ab-knockout (IL-1a2/2 and IL-1ab 2/2 fibrosarcoma lines express MHC class I molecules at a high level. The lines do not differ in their susceptibility toward NK cells, macrophages, and allogeneic CTL, or in their capacity as stimulators of an allogeneic response. However, IL-1b 2/2 tumors rarely grow in the syngeneic host, which is the consequence of a strong T helper and CTL response induction by IL-1a-competent, IL-1b À=À tumors. On the other hand, IL-1b-competent, IL-1aÀ=À tumors strongly assist CD11b 1 Gr-1 1 myeloid-derived suppressor cell and regulatory T cell expansion, which both suppress with high efficacy activated T helper cell proliferation and CTL lysis. In IL-1ab À=À tumors, the absence of IL-1a becomes decisive, i.e. despite reduced suppressor cell recruitment, tumor growth was unimpaired due to inefficient immune response induction. Thus, sarcoma cell-derived IL-1a and IL-1b do not act in concert. Induction of a strong immune response by IL-1a demands therapeutic exploitation, which may become more efficient if systemic induction of immunosuppression by IL-1b can also be circumvented.