Opposing effects of fibrosarcoma cell-derived IL-1α and IL-1β on immune response induction

✍ Scribed by Rachid Marhaba; Irina Nazarenko; Daniela Knöfler; Eli Reich; Elena Voronov; Mario Vitacolonna; Dagmar Hildebrand; Elena Elter; Ron N. Apte; Margot Zöller

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: French
• Weight: 777 KB
• Volume: 123
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23503

✦ Synopsis

Abstract

There is evidence that cell‐associated IL‐1α 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‐1α‐, IL‐1β‐ or IL‐1aβ‐knockout (IL‐1α^−/−^, IL‐1β^−/−^, IL‐1αβ^−/−^) C57BL6 mice. The wt, IL‐1α^−/−^, IL‐1β^−/−^ and IL‐1αβ^−/−^ 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‐1β^−/−^ tumors rarely grow in the syngeneic host, which is the consequence of a strong T helper and CTL response induction by IL‐1α‐competent, IL‐1β^−/−^ tumors. On the other hand, IL‐1β‐competent, IL‐1α^−/−^ tumors strongly assist CD11b^+^Gr‐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‐1αβ^−/−^ tumors, the absence of IL‐1α becomes decisive, i.e. despite reduced suppressor cell recruitment, tumor growth was unimpaired due to inefficient immune response induction. Thus, sarcoma cell‐derived IL‐1α and IL‐1β do not act in concert. Induction of a strong immune response by IL‐1α demands therapeutic exploitation, which may become more efficient if systemic induction of immunosuppression by IL‐1β can also be circumvented. © 2008 Wiley‐Liss, Inc.