title: Inflammasome activation is critical to the protective immune response during chemically induced squamous cell carcinoma.
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.
authors.affiliation: Department of Biological Sciences - Microbiology and Immunology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Thais Helena
authors.initials: TH
authors.lastname: Gasparoto
authors.affiliation: Department of Biological Sciences - Microbiology and Immunology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil; Department of Stomatology - Oral Pathology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Carine Ervolino
authors.initials: CE
authors.lastname: de Oliveira
authors.affiliation: Department of Biological Sciences - Microbiology and Immunology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Luisa Thomazini
authors.initials: LT
authors.lastname: de Freitas
authors.affiliation: Department of Biological Sciences - Microbiology and Immunology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Claudia Ramos
authors.initials: CR
authors.lastname: Pinheiro
authors.affiliation: Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Juliana Issa
authors.initials: JI
authors.lastname: Hori
authors.affiliation: Department of Biological Sciences - Microbiology and Immunology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Departament of Pathology, Medical School, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Karen Angélica
authors.initials: KA
authors.lastname: Cavassani
authors.affiliation: Laboratorio de Mecanismos Moleculares de Carcinogénesis, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Buenos Aires, Argentina.
authors.forename: Roxana
authors.initials: R
authors.lastname: Schillaci
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: João Santana
authors.initials: JS
authors.lastname: da Silva
authors.affiliation: Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Dario Simões
authors.initials: DS
authors.lastname: Zamboni
authors.affiliation: Department of Biological Sciences - Microbiology and Immunology, Bauru School of Dentistry, University of São Paulo, Bauru, SP, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campanelli
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000276:immunology*; D005260:Female; D058847:Inflammasomes / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010212:Papilloma / Q000139:chemically induced / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D015127:9,10-Dimethyl-1,2-benzanthracene