Abstract
Chronic Inflammation in tumor microenvironments is not only associated with various stages of tumor development, but also has significant impacts on tumor immunity and immunotherapy. Inflammasome are an important innate immune pathway critical for the production of active IL-1β and interleukin 18, as well as the induction of pyroptosis. Although extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer. However, very recent studies demonstrate that inflammasomes promote tumor progression in skin and breast cancer. These results indicate that inflammasomes can promote and suppress tumor development depending on types of tumors, specific inflammasomes involved, and downstream effector molecules. The complicated role of inflammasomes raises new opportunities and challenges to manipulate inflammasome pathways in the treatment of cancer.
Highlights
Emerging evidence indicates that chronic inflammation plays an important role at all stages of tumor development, including initiation, growth, invasion, and metastasis [1,2,3,4,5,6,7]
Production of mature or active IL-1β needs two signals: the first signal is initiated by toll-like receptors (TLRs) ligands or endogenous molecules to induce the expression of pro-IL-1β proteins; the second is triggered by very diverse stimuli activating inflammasomes, leading to caspase-1-dependent conversion of pro-IL-1β to mature IL-1β
Results show that mice deficient for a caspase recruitment domain (ASC) in myeloid cells are protected from DMBA/TPA-induced skin cancer, suggesting a tumor-promoting role of inflammasomes and IL-1R signaling in myeloid cells
Summary
Chronic Inflammation in tumor microenvironments is associated with various stages of tumor development, and has significant impacts on tumor immunity and immunotherapy. Extensive studies have demonstrated that inflammasomes play a vital role in infectious and autoimmune diseases, their role in tumor progression remains elusive. Multiple studies using a colitis-associated colon cancer model show that inflammasome components provide protection against the development of colon cancer. Very recent studies demonstrate that inflammasomes promote tumor progression in skin and breast cancer. These results indicate that inflammasomes can promote and suppress tumor development depending on types of tumors, specific inflammasomes involved, and downstream effector molecules.
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