Inflammasome activation is critical to the protective immune response during chemically induced squamous cell carcinoma

• Published in: PloS one Vol. 9; no. 9; p. e107170
• Main Authors: Gasparoto, Thais Helena, de Oliveira, Carine Ervolino, de Freitas, Luisa Thomazini, Pinheiro, Claudia Ramos, Hori, Juliana Issa, Garlet, Gustavo Pompermaier, Cavassani, Karen Angélica, Schillaci, Roxana, da Silva, João Santana, Zamboni, Dario Simões, Campanelli, Ana Paula
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.09.2014; Public Library of Science (PLoS)
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Activation; Animals; Antitumor activity; Apoptosis; Biology; Biology and Life Sciences; Cancer; Carcinoma, Squamous Cell - chemically induced; Carcinoma, Squamous Cell - immunology; Caspase; CD25 antigen; CD4 antigen; CD45RB antigen; CD8 antigen; Cytokines; Dentistry; Elastase; Female; Foxp3 protein; Immune response; Immune system; Immunology; Inflammasomes; Inflammasomes - physiology; Inflammation; Interferon; Interleukin 18; Lesions; Leukocytes (neutrophilic); Lymph nodes; Lymph Nodes - immunology; Lymphocytes; Lymphocytes T; Macrophages; Medical schools; Medicine and Health Sciences; Metastases; Mice; Mice, Inbred C57BL; Mice, Knockout; Natural killer cells; Papilloma; Papilloma - chemically induced; Papilloma - immunology; Peroxidase; Proteins; Recruitment; Skin Neoplasms - immunology; Squamous cell carcinoma; T cell receptors; Tumor necrosis factor-α; Tumorigenesis; Tumors; Brazil; Argentina
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107170

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.