AccScience Publishing / CP / Online First / DOI: 10.36922/CP025310046
REVIEW ARTICLE

Interleukin-1 beta signaling in cancer: A double-edged sword in inflammation and tumorigenesis

Vural Yilmaz1*
Show Less
1 Department of Basic Sciences and Humanities, Faculty of Arts and Sciences, Cyprus International University, Nicosia, Northern Cyprus, Türkiye
Received: 28 July 2025 | Revised: 26 August 2025 | Accepted: 1 September 2025 | Published online: 14 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Interleukin-1 beta (IL-1β) is a central pro-inflammatory cytokine with critical roles in immune regulation, inflammation, and tumor biology. Synthesized as an inactive precursor and activated through inflammasome-mediated cleavage, IL-1β signals via the IL-1 receptor to orchestrate immune responses. While essential for host defense, sustained IL-1β activity in the tumor microenvironment promotes angiogenesis, metastasis, epithelial–mesenchymal transition, and immune suppression, thereby facilitating the progression of cancers such as breast, lung, pancreatic, and colorectal. Conversely, IL-1β can enhance anti-tumor immunity by driving dendritic cell maturation, T-cell priming, and pyroptosis, thereby contributing to beneficial immune surveillance in certain hematologic malignancies. This dual role presents both challenges and opportunities for therapeutic intervention. Clinical blockade of IL-1β with agents such as anakinra, canakinumab, and rilonacept has shown promise, notably in the CANTOS trial, where IL-1β inhibition was associated with a reduction in lung cancer incidence. However, outcomes in colorectal and pancreatic cancer remain variable. The potential for immune suppression, combined with the absence of predictive biomarkers, underscores the need for precision-based strategies. Emerging approaches, including serum and tissue IL-1β profiling, analysis of inflammasome components, liquid biopsy, spatial transcriptomics, and single-cell technologies, may enable context-specific modulation. This review synthesizes current understanding of IL-1β’s paradoxical functions in cancer, evaluates therapeutic strategies targeting its signaling axis, and highlights future directions for integrating IL-1β modulation into precision oncology.

Keywords
Interleukin-1 beta
Cancer
Inflammation
Tumor microenvironment
Cytokines
Immunotherapy
Pyroptosis
Funding
None.
Conflict of interest
The author declares no conflict of interest.
References
  1. Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8-27. doi: 10.1111/imr.12621

 

  1. Weber A, Wasiliew P, Kracht M. Interleukin-1 (IL-1) pathway. Sci Signal. 2010;3(105):cm1. doi: 10.1126/scisignal.3105cm1

 

  1. Greten FR, Grivennikov SI. Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity. 2019;51(1):27-41. doi: 10.1016/j.immuni.2019.06.025

 

  1. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436-444. doi: 10.1038/nature07205

 

  1. Filippi I, Carraro F, Naldini A. Interleukin-1β affects MDA-MB-231 breast cancer cell migration under hypoxia: Role of HIF-1α and NFκB transcription factors. Mediators Inflamm. 2015;2015:789414. doi: 10.1155/2015/789414

 

  1. Wang H, Luo J, Zhang T, et al. IL-1β promotes immune suppression and epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma. Front Oncol. 2021;11:669619. doi: 10.3389/fonc.2021.669619

 

  1. Kantola T, Klintrup K, Väyrynen JP, et al. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. Br J Cancer. 2012;107(10):1729-1736. doi: 10.1038/bjc.2012.456

 

  1. Di Paolo NC, Shayakhmetov DM. Interleukin 1α and the inflammatory process. Nat Immunol. 2016;17(8):906-913. doi: 10.1038/ni.3503

 

  1. Benetti R, Tommasini A, Ronfani L. IL-1β expression in tumor-associated macrophages fuels immune checkpoint resistance in melanoma. Nat Commun. 2022;13(1):1145. doi: 10.1038/s41467-022-28828-7

 

  1. Wesa AK, Galy A. IL-1β induces dendritic cells to produce IL-12. Int Immunol. 2001;13(8):1053-1061. doi: 10.1093/intimm/13.8.1053

 

  1. Xia X, Wang X, Cheng Z, Qin W, Lei L, Jiang J. The role of pyroptosis in cancer: Pro-cancer or pro-host? Cell Death Dis. 2019;10(9):650. doi: 10.1038/s41419-019-1870-1

 

  1. Zhang Z, Zhang Y, Xia S, et al. Gasdermin E suppresses tumor growth by activating anti-tumor immunity. Nature. 2020;579(7799):415-420. doi: 10.1038/s41586-020-2071-9

 

  1. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633-652. doi: 10.1038/nrd3800

 

  1. Ridker PM, Howard CP, Walter V, et al. Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, and interleukin-6: A phase IIb randomized, placebo-controlled trial. Lancet. 2012;380(9850):815-826. doi: 10.1016/S0140-6736(12)60648-9

 

  1. López-Castejón G, Brough D. Understanding the mechanism of IL-1β secretion. Cytokine Growth Factor Rev. 2011;22(4):189-195. doi: 10.1016/j.cytogfr.2011.10.001

 

  1. Tsuchiya K, Nakajima S, Hosojima S, et al. Caspase-1 initiates apoptosis in the absence of gasdermin D. Nat Commun. 2019;10(1):2091. doi: 10.1038/s41467-019-10052-x

 

  1. Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477-489. doi: 10.1038/s41577-019-0165-0

 

  1. Heilig R, Dick MS, Sborgi L, Meunier E, Hiller S, Broz P. The gasdermin-D pore acts as a conduit for IL-1β secretion. Cell. 2018;173(3):667-679.e14. doi: 10.1016/j.cell.2018.03.025

 

  1. Evavold CL, Ruan J, Tan Y, Xia S, Wu H, Kagan JC. The pore-forming protein gasdermin D regulates interleukin-1 secretion from living macrophages. Immunity. 2018;48(1):35-44.e6. doi: 10.1016/j.immuni.2017.11.013

 

  1. Monteleone M, Stow JL, Schroder K. Mechanisms of unconventional secretion of IL-1 family cytokines. Cytokine. 2015;74(2):213-218. doi: 10.1016/j.cyto.2015.03.022

 

  1. O’Neill LAJ, Golenbock D, Bowie AG. The history of Toll-like receptors-redefining innate immunity. Nat Rev Immunol. 2013;13(6):453-460. doi: 10.1038/nri3446

 

  1. Ridderstad Wollberg A, Laan M, van Rijt L, et al. Interleukin-1 signaling in the pathogenesis of cancer. Cancers (Basel). 2023;15(4):1032. doi: 10.3390/cancers15041032

 

  1. Akdis M, Aab A, Altunbulakli C, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138(4):984-1010. doi: 10.1016/j.jaci.2016.06.033

 

  1. Arend WP. The balance between IL-1 and IL-1Ra in disease. Cytokine Growth Factor Rev. 2002;13(4-5):323-340. doi: 10.1016/S1359-6101(02)00026-5

 

  1. Zarezadeh Mehrabadi A, Aghamohamadi N, Khoshmirsafa M, et al. The roles of interleukin-1 receptor accessory protein in certain inflammatory conditions. Immunology. 2022;166(1):38-46. doi: 10.1111/imm.13462

 

  1. Vereecke L, Beyaert R, van Loo G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol. 2009;30(8):383-391. doi: 10.1016/j.it.2009.05.007

 

  1. Quinn SR, O’Neill LA. A trio of microRNAs that control Toll-like receptor signalling. Int Immunol. 2011;23(7):421-425. doi: 10.1093/intimm/dxr034

 

  1. Voronov E, Apte RN. IL-1 in colon inflammation, colon carcinogenesis and invasiveness of colon cancer. Cancer Microenviron. 2015;8(3):187-200. doi: 10.1007/s12307-015-0171-6

 

  1. Fang M, Yuan J, Peng C, Li Y. Collagen as a double-edged sword in tumor progression. Tumour Biol. 2014;35(4):2871-2882. doi: 10.1007/s13277-013-1511-7

 

  1. Tulotta C, Lefley DV, Moore CK, et al. IL-1B drives opposing responses in primary tumours and bone metastases; harnessing combination therapies to improve outcome in breast cancer. NPJ Breast Cancer. 2021;7(1):95. doi: 10.1038/s41523-021-00305-w

 

  1. Cocco C, Amodeo R, Azzi C, et al. IL-1β expression correlates with tumor aggressiveness and immune infiltration in human colorectal cancer. Cancer Immunol Immunother. 2022;71(3):579-591. doi: 10.1007/s00262-021-02928-z

 

  1. Gabrilovich DI. Myeloid-derived suppressor cells. Cancer Immunol Res. 2017;5(1):3-8. doi: 10.1158/2326-6066.CIR-16-0297

 

  1. Wang L, Chang EW, Wong SC, Ong SM, Chong DQ, Ling KL. Increased IL-1β expression in infiltrating CD68+ macrophages is associated with poor response to immune checkpoint blockade in gastric cancer. Oncoimmunology. 2019;8(10):e1621376. doi: 10.1080/2162402X.2019.1621376

 

  1. Zelenay S, van der Veen AG, Böttcher JP, et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell. 2015;162(6):1257-1270. doi: 10.1016/j.cell.2015.08.015

 

  1. Van Houtte L, Verhoeven Y, Van Puyvelde H, et al. Crosstalk between IL-1 family members and cancer: From basic biology to therapeutic perspectives. Front Immunol. 2021;12:742720. doi: 10.3389/fimmu.2021.742720

 

  1. Wu Y, Zhou BP. TNF-α/NF-κB/Snail pathway in cancer cell migration and invasion. Br J Cancer. 2010;102(4):639-644. doi: 10.1038/sj.bjc.6605530

 

  1. Huber MA, Azoitei N, Baumann B, et al. NF-κB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression. J Clin Invest. 2004;114(4):569-581. doi: 10.1172/JCI21074

 

  1. Kaler P, Godasi BN, Augenlicht L, Klampfer L. The NF-κB/ IL-6 pathway is a major mediator of the inflammatory response to altered gut microbiota in colon cancer. Clin Cancer Res. 2014;20(5):1202-1212. doi: 10.1158/1078-0432.CCR-13-2572

 

  1. Erez N, Truitt M, Olson P, Arron ST, Hanahan D. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-κB-dependent manner. Cancer Cell. 2010;17(2):135-147. doi: 10.1016/j.ccr.2009.12.041

 

  1. Costa A, Scholer-Dahirel A, Mechta-Grigoriou F. The role of reactive oxygen species and metabolism on cancer-associated fibroblasts in promoting tumor aggressiveness. Antioxid Redox Signal. 2014;21(5):738-756. doi: 10.1089/ars.2013.5594

 

  1. Sahai E, Astsaturov I, Cukierman E, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20(3):174-186. doi: 10.1038/s41568-019-0238-1

 

  1. Chen L, Fan J, Chen H, et al. The IL-1β pathway is associated with the pathogenesis and progression of triple-negative breast cancer. J Cell Mol Med. 2019;23(8):5271-5279. doi: 10.1111/jcmm.14347

 

  1. Terzic J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138(6):2101-2114.e5. doi: 10.1053/j.gastro.2010.01.058

 

  1. Tang L, Qian Y, Li Y, et al. Interleukin-1β promotes non-small cell lung cancer cell proliferation and migration via upregulation of miR-425-5p. Mol Med Rep. 2021;24(2):1-8. doi: 10.3892/mmr.2021.12185

 

  1. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab and incident lung cancer in patients with atherosclerosis: Exploratory results from a randomized, double-blind, placebo-controlled trial. Lancet. 2017;390(10105):1833-1842. doi: 10.1016/S0140-6736(17)32247-X

 

  1. Ben-Sasson SZ, Hu-Li J, Quiel J, et al. IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A. 2009;106(17):7119-7124. doi: 10.1073/pnas.0902745106

 

  1. Ichiba M, Nakajima H, Shibata Y, et al. IL-1β enhances antigen presentation by dendritic cells through induction of CD40 and CD86 expression. Immunobiology. 2020;225(2):151865. doi: 10.1016/j.imbio.2019.151865

 

  1. Kondo T, Takata H, Matsuki F, Takiguchi M. Cutting edge: IL-1 receptor signaling is critical for the development of memory CD8+ T cells. J Immunol. 2006;177(9):5730-5734. doi: 10.4049/jimmunol.177.9.5730

 

  1. Weiden J, Tel J, Figdor CG. Synthetic immune niches for cancer immunotherapy. Nat Rev Immunol. 2018;18(4):212-219. doi: 10.1038/nri.2017.126

 

  1. Fang Y, Tian S, Pan Y, et al. Pyroptosis: A new frontier in cancer. Biomed Pharmacother. 2020;121:109595. doi: 10.1016/j.biopha.2019.109595

 

  1. Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015;526(7575):660-665. doi: 10.1038/nature15514

 

  1. Hou J, Zhao R, Xia W, et al. PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis. Nat Cell Biol. 2020;22(10):1264-1275. doi: 10.1038/s41556-020-0575-z

 

  1. Erkes DA, Cai W, Sanchez IM, et al. Mutant BRAF and MEK inhibitors regulate the tumor immune microenvironment via pyroptosis. Cancer Discov. 2020;10(2):254-269. doi: 10.1158/2159-8290.CD-19-0779

 

  1. Carey A, Edwards DK, Eide CA, et al. Identification of interleukin-1 by functional screening as a key mediator of cellular expansion and disease progression in acute myeloid leukemia. Cell Rep. 2017;18(13):3204-3218. doi: 10.1016/j.celrep.2017.03.004

 

  1. Rensing-Ehl A, Malissen B, Regamey N, Ehl S. CD8+ T cell-mediated control of Epstein-Barr virus infection in X-linked lymphoproliferative disease. J Exp Med. 2002;195(6):765-774. doi: 10.1084/jem.20012087

 

  1. Tawara I, Kondo T, Yoshimura S, et al. Interleukin-1 blockade attenuates graft-versus-host disease while preserving the graft-versus-leukemia effect. Blood. 2011;117(20):5405-5414. doi: 10.1182/blood-2010-11-319160

 

  1. Fleischmann RM, Schechtman J, Bennett R, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, in the treatment of rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum. 2003;48(4):927-934. doi: 10.1002/art.10807

 

  1. West NR, McCuaig S, Franchini F, Powrie F. Emerging cytokine networks in colorectal cancer. Nat Rev Immunol. 2015;15(10):615-629. doi: 10.1038/nri3896

 

  1. Tabernero J, Dirix L, Schoffski P, et al. A phase I, open-label study to assess safety and pharmacokinetics of canakinumab in patients with advanced solid tumors. Clin Transl Oncol. 2013;15(5):407-413. doi: 10.1007/s12094-012-0949-2

 

  1. Tarp S, Jensen ML, Kristensen LE, et al. Efficacy and safety of rilonacept for treatment of inflammatory disorders: A systematic review. Clin Rheumatol. 2014;33(5):679-688. doi: 10.1007/s10067-013-2390-1

 

  1. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131. doi: 10.1056/NEJMoa1707914

 

  1. Garon EB, Lu S, Goto Y, et al. Canakinumab as adjuvant therapy in patients with completely resected non-small-cell lung cancer: Results from the CANOPY-A double-blind, randomized clinical trial. J Clin Oncol. 2024;42(2):180-191. doi: 10.1200/JCO.23.00910

 

  1. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of cancer. Blood. 2011;117(14):3720-3732. doi: 10.1182/blood-2010-07-273417

 

  1. Holen I, Lefley DV, Francis SE, et al. IL-1 drives breast cancer growth and bone metastasis in vivo. Oncotarget. 2016;7(48):75571-75584. doi: 10.18632/oncotarget.12566

 

  1. Daley D, Mani VR, Mohan N, et al. NLRP3 signaling drives macrophage-induced adaptive immune suppression in pancreatic carcinoma. J Exp Med. 2017;214(6):1711-1724. doi: 10.1084/jem.20161708

 

  1. Greten FR, Grivennikov SI. Inflammation and immunity in cancer development. Nat Rev Immunol. 2019;19(3):195-208. doi: 10.1038/s41577-018-0081-x

 

  1. Kaplanov I, Carmi Y, Kornetsky R, et al. Blocking IL-1β reverses the immunosuppressive tumor microenvironment and enhances antitumor immunity. Cancer Immunol Res. 2019;7(4):509-520. doi: 10.1158/2326-6066.CIR-18-0489

 

  1. Schmid MC, Khan SQ, Kaneda MM, et al. Integrin CD11b activation drives anti-tumor innate immunity. Nat Commun. 2018;9(1):5379. doi: 10.1038/s41467-018-07850-1

 

  1. Li X, Yao W, Yuan Y, et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut. 2017;66(1):157-167. doi: 10.1136/gutjnl-2015-310514

 

  1. Protti MP, De Monte L. Cross-talk within the tumor microenvironment mediates Th2-type inflammation in pancreatic cancer. Oncoimmunology. 2012;1(1):89-91. doi: 10.4161/onci.1.1.18423

 

  1. Tulotta C, Ottewell P. The role of IL-1B in breast cancer bone metastasis. Endocr Relat Cancer. 2018;25(7):R421-R434. doi: 10.1530/ERC-18-0080

 

  1. Tabernero J, Melero I, Ros W, et al. Canakinumab in combination with spartalizumab in patients with advanced solid tumors: A phase Ib study. Clin Cancer Res. 2022;28(10):2089-2098. doi: 10.1158/1078-0432.CCR-21-3816

 

  1. Wensveen FM, Jelencic V, Polic B. NKG2D: A master regulator of immune cell responsiveness. Front Immunol. 2018;9:441. doi: 10.3389/fimmu.2018.00441

 

  1. Cavalli G, Dinarello CA. Anakinra therapy for non-cancer inflammatory diseases. Front Pharmacol. 2018;9:1157. doi: 10.3389/fphar.2018.01157

 

  1. Koebel CM, Vermi W, Swann JB, et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007;450(7171):903-907. doi: 10.1038/nature06309

 

  1. Apetoh L, Ghiringhelli F, Tesniere A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13(9):1050-1059. doi: 10.1038/nm1622

 

  1. Okamoto M, Liu W, Luo Y, et al. Constitutively active inflammasome in human melanoma cells mediating autoinflammation via caspase-1 processing and secretion of interleukin-1β. J Biol Chem. 2010;285(9):6471-6487. doi: 10.1074/jbc.M109.064907

 

  1. Moncada R, Barkley D, Wagner F, et al. Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas. Nat Biotechnol. 2020;38(3):333-342. doi: 10.1038/s41587-019-0392-8

 

  1. Mills CD. Anatomy of a discovery: M1 and M2 macrophages. Front Immunol. 2015;6:212. doi: 10.3389/fimmu.2015.00212

 

  1. Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019;18(3):175-196. doi: 10.1038/s41573-018-0006-z

 

  1. Rao A, Barkley D, França GS, Yanai I. Exploring tissue architecture using spatial transcriptomics. Nature. 2021;596(7871):211-220. doi: 10.1038/s41586-021-03634-9

 

  1. Elyada E, Bolisetty M, Laise P, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 2019;9(8):1102-1123. doi: 10.1158/2159-8290.CD-19-0094

 

  1. Gu M, Zhu B, Hu L, et al. Novel insights into IL-37: An anti-inflammatory cytokine with therapeutic potential. Front Immunol. 2023;14:1278521. doi: 10.3389/fimmu.2023.1278521

 

  1. Helmink BA, Reddy SM, Gao J, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020;577(7791):549-555. doi: 10.1038/s41586-019-1922-8

 

  1. Tapia-Abellán A, Angosto-Bazarra D, Martínez-Banaclocha H, et al. MCC950 closes the active conformation of NLRP3 to an inactive state. Nat Chem Biol. 2019;15(6):560-564. doi: 10.1038/s41589-019-0278-6

 

  1. Wang H, Hu S, Chen X, et al. IL-1 signaling in the tumor microenvironment and its potential as a therapeutic target in cancer. Front Oncol. 2023;13:1111653. doi: 10.3389/fonc.2023.1111653

 

  1. Caronni N, Savino B, Recordati C, et al. IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer. Nature. 2023;618(7965):145-152. doi: 10.1038/s41586-023-06078-7

 

  1. Chen J, Wang X, Li Y, et al. IL-1β promotes esophageal squamous cell carcinoma growth and metastasis through FOXO3A by activating the PI3K/AKT pathway. Cell Death Discov. 2024;10:25. doi: 10.1038/s41420-024-01722-9

 

  1. Khawkhiaw K, Panaampon J, Imemkamon T, Saengboonmee C. Interleukin-1β: Friend or foe for gastrointestinal cancers. World J Gastrointest Oncol. 2024;16(5):1676-1682. doi: 10.4251/wjgo.v16.i5.1676

 

  1. Ohkuri T, Kosaka A, Ishibashi K, et al. Intratumoral administration of STING agonist enhances the efficacy of anti-programmed death-1 antibody in murine tumor models. Cancer Immunol Res. 2017;5(8):661-672. doi: 10.1158/2326-6066.CIR-16-0304
Share
Back to top
Cancer Plus, Electronic ISSN: 2661-3840 Print ISSN: 2661-3832, Published by AccScience Publishing