IL1α Antagonizes IL1β and Promotes Adaptive Immune Rejection of Malignant Tumors.

Abstract:

:We assessed the contribution of IL1 signaling molecules to malignant tumor growth using IL1β-/-, IL1α-/-, and IL1R1-/- mice. Tumors grew progressively in IL1R-/- and IL1α-/- mice but were often absent in IL1β-/- mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true across multiple distinct tumor lineages. Antibodies to IL1β prevented tumor growth in wild-type (WT) mice but not in IL1R1-/- or IL1α-/- mice. Antibodies to IL1α promoted tumor growth in IL1β-/- mice and reversed the tumor-suppressive effect of anti-IL1β in WT mice. Depletion of CD8+ T cells and blockade of lymphocyte mobilization abrogated the IL1β-/- tumor suppressive effect, as did crossing IL1β-/- mice to SCID or Rag1-/- mice. Finally, blockade of IL1β synergized with blockade of PD-1 to inhibit tumor growth in WT mice. These results suggest that IL1β promotes tumor growth, whereas IL1α inhibits tumor growth by enhancing T-cell-mediated antitumor immunity.

journal_name

Cancer Immunol Res

authors

Tian T,Lofftus S,Pan Y,Stingley CA,King SL,Zhao J,Pan TY,Lock R,Marglous JW,Liu K,Widlund HR,Fuhlbrigge RC,Cichowski K,Kupper TS

doi

10.1158/2326-6066.CIR-19-0552

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

660-671

issue

5

eissn

2326-6066

issn

2326-6074

pii

2326-6066.CIR-19-0552

journal_volume

8

pub_type

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