Inflammasomes and Cancer: The Dynamic Role of the Inflammasome in Tumor Development

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.

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

“…In addition to the crucial roles in inflammatory and immune responses, emerging evidence has indicated that inflammasomes components are markedly upregulated in various cancers, such as lung, melanoma, oral squamous cell carcinoma, and breast cancer cells [18][19][20][21][22]. In addition, activation of the inflammasome facilitates tumor progression [23,24], suggesting that inflammasomes act as mediators that bridge chronic inflammation and tumorigenesis. Interestingly, in contrast to this notion, it has been also well documented that the suppressive effects on tumor growth by various anticancer agents are mediated through inflammasomes activation, which initiates pyroptotic cell death in cancer cells [25][26][27].…”

Dual Role of Inflammasome Adaptor ASC in Cancer

“…(B) Pro-inflammatory function in cancer cells. In cancer cells and myeloid cells (such as TAMs), recognition of pathogen-or damage-associated molecular patterns (PAMPs, DAMPs) induces the assembly/polymerization of the inflammasome molecular complex, which in cancer cells is otherwise often constitutively activated as a result of genetic lesions (Kolb et al, 2014;Kantono and Guo, 2017;Karan, 2018;Karki and Kanneganti, 2019). The inflammasome is composed by a multimerized module formed by a sensor Nod Leucine-Rich Repeat-containing receptor, such as NLRP3, bound to the pyrin domain of the adaptor ASC, which in turn is bound, through its CARD domain, to pro-caspase-1.…”

“…The role of inflammasomes in cancer has been recently discussed elsewhere (Kolb et al, 2014;Kantono and Guo, 2017;Karan, 2018;Karki and Kanneganti, 2019;Van Gorp and Lamkanfi, 2019). We refer readers interested in comprehensive summaries of the field to those reviews.…”

NLRP1 and NLRP3 inflammasomes as a new approach to skin carcinogenesis (Review)

“…An increasing body of evidence indicates that inflammation is one of the hallmarks of carcinogenesis, allowing the growth and metastasis of tumors (1). The role of inflammation is two-fold: On one hand, the tumor and antigens present on the surface of cells can stimulate effector cell recruitment of the innate immune system, resulting in the destruction of diseased tissue; on the other hand, mere stimulation of the immune response is associated with the development of inflammation, which can stimulate the growth of a tumor through the production of proinflammatory cytokines, thus creating a feedback loop (2). A special role in this process is played by interleukin 1β (IL-1β), which promotes tumor progression, neoangiogenesis, and metastasis (3).…”