Abstract
Chronic inflammation affects most stages of tumorigenesis, including initiation, promotion, malignant differentiation, invasion and metastasis. Inflammasomes have been described as involved with persistent inflammation and are known to exert both pro and antitumour effects. We evaluated the influence of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase (CASP)-1 in the antitumor immune response using a multistage model of squamous cell carcinoma (SCC) development. Absence of ASC and CASP-1 resulted in an earlier incidence and increased number of papilloma. Loss of inflammassome function in mice resulted in decreased presence of natural killer (NK), dendritic (DC), CD4+, CD8+ and CD45RB+ T cells in the tumor lesions as well as in lymph nodes (LN) compared with WT mice. Increased percentage of CD4+CD25+Foxp3+ T cells was associated with association with inflammasome loss of function. Moreover, significant differences were also found with neutrophils and macrophage infiltrating the lesions. Myeloperoxidase (MPO), but not elastase (ELA), activity oscillated among the groups during the SCC development. Levels of proinflammatory cytokines IL-1β, IL-18, Tumor Necrosis Factor (TNF)-α and Interferon (IFN)-γ were decreased in the tumor microenvironment in the absence of inflammasome proteins. These observations suggest a link between inflammasome function and SCC tumorigenesis, indicating an important role for inflammasome activation in the control of SCC development.
Highlights
An effective immune response is important to restrict the development of the disease, mainly via induction, function, and regulation of effector lymphocytes [1,2]
Data obtained from this study shows the effect of adaptor proteins a caspase recruitment domain (ASC) and the enzyme CASP-1 in the protection against squamous cell carcinoma (SCC) tumorigenesis and progression
Such inflammasome dependence was probably associated with the development of a suppressed immune response impairing the influx of T cells (Ts) and natural killer (NK) cells into the lesions as well as an antitumor response in the lymph nodes
Summary
An effective immune response is important to restrict the development of the disease, mainly via induction, function, and regulation of effector lymphocytes [1,2]. In spite of crucial role of T cells in cancer immunosurveillance, the innate immunity plays an important part in the development and control of tumor response [8,9]. Inflammasomes are a set of intracellular protein complexes that enable autocatalytic activation of inflammatory caspases, as caspase-1, which drive host immune responses by releasing proinflammatory cytokines and inducing pyroptosis [11]. Their activation occurs in response to pathogens (PAMPs) and stress or danger signals (DAMPs) promoting the maturation of cytokines of the IL-1 family: IL-1b and IL-18 [12,13]. Different studies have been showing the important role of IL-18 as the primary IFN-c inducing cytokine and responsible to promote a Th1 response [14,15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
