Understand what facilitates Pro-Tumor Inflammation and how it may help create a microenvironment for cancer in the body1-6

 

The Role of Pro-Tumor Inflammation (PTI)

Through inflammatory mediators, PTI is believed to:

Facilitate oncogenic processes, promoting tumor cell growth and proliferation7,8

  • An inflammatory environment may increase mutation rates and initiate the production of growth factors and cytokines7
  • PTI can induce growth factors and facilitate angiogenesis, leading to tumor cell proliferation9

Help suppress the immune response to cancer by altering the tumor microenvironment7,8

Image illustrating how PTI drives oncogenic processes and suppresses immune system response

Overview of the Tumor Microenvironment

Image illustrating the tumor microenvironment

As a tumor grows it develops its own ecosystem, known as the tumor microenvironment. Among other functions, the tumor microenvironment helps the tumor survive by shielding it from the immune system, in part through the recruitment of immunosuppressive cells such as regulatory T cells (Tregs), macrophages, and myeloid-derived suppressor cells (MDSCs) that suppress cytotoxic T cells.4-6

Role of Interleukin-1 Beta (IL-1β)

Interleukin-1 beta (IL-1β) plays a role in PTI10

There is preliminary evidence that IL-1β helps facilitate PTI by activating tumor processes and recruiting immunosuppressive cells.1-3

IL-1β signaling contributes to tumor growth and proliferation through the activation of numerous transcription factors, including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)2,11

IL-1β contributes to the suppression of the immune response against tumor cells by recruiting immunosuppressive cells to the tumor microenvironment. Infiltrating MDSCs, Tregs, and tumor-associated macrophages (TAMs) contribute to the deactivation of cytotoxic T cells in the tumor microenvironment2,12

Preclinical data support that IL-1β, a cytokine in the tumor microenvironment, is one of the drivers of PTI required for tumor growth, tumor survival, and the development of metastasis.3,13  

Image illustrating how PTI drives oncogenic processes and suppresses immune system response

Multiple other cell types and cytokines are also implicated, such as macrophages, interleukins, and tumor necrosis factor–alpha (TNF-α).7

 

According to preliminary evidence, IL-1β expression can be elevated in patients with non-small cell lung cancer and may correlate with poor prognosis.14-16

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References:
 1. Takahashi H, Sakakura K, Kudo T, et al. Oncotarget. 2017;8(5):8633-8647.
 2. Chaudhry SI, Hooper S, Ny E, et al. Oncogene. 2013;32(6):747-758.
 3. Bunt SK, Sinha P, Clements VK, et al. J Immunol. 2006;176(1):284-290.
 4. Demaria S. Cancer Immunotherapy. 2013:149-164.
 5. Joyce JA, Fearon DT. Science. 2015;348(6230):74-80.
 6. Jin MZ, Jin WL. Signal Transduct Target Ther. 2020;5(1):166. 
 7. Grivennikov SI, Greten FR, Karin M. Cell. 2010;140(6):883-889.
 8. Greten FR, Grivennikov SI. Immunity. 2019;51(1):27-41. 
 9. Hanahan D, Weinberg RA. Cell. 2011;144(5):646-674.
10. Carmi Y, Dotan S, Rider P, et al. J Immunol. 2013;190(7):3500-3509.
11. Taniguchi K, Karin M. Nat Rev Immunol. 2018;18(5):309-324.
12. Yano S, Nokihara H, Yamamoto A, et al. Cancer Sci. 2003;94(3):244-252.
13. Chen L, Huang CF, Li YC, et al. Cell Mol Life Sci. 2018;75(11):2045-2058.
14. Elaraj DM, Weinreich DM, Varghese S, et al. Clin Cancer Res. 2006;12(4):1088-1096.
15. Kim JW, Koh Y, Kim DW, et al. Cancer Res Treat. 2013;45(4):325-333.
16. Millares L, Barreiro E, Cortes R, et al. Lung Cancer. 2018;122:124-130.