Inflammasome Activation Is Critical to the Protective Immune Response during Chemically Induced Squamous Cell Carcinoma

Author(s):Show less -

Gasparoto, Thais Helena ^[1] ; de Oliveira, Carine Ervolino ^{[1, 2]} ; de Freitas, Luisa Thomazini ^[1] ; Pinheiro, Claudia Ramos ^[1] ; Hori, Juliana Issa ^[3] ; Garlet, Gustavo Pompermaier ^[1] ; Cavassani, Karen Angelica ^[4] ; Schillaci, Roxana ^[5] ; da Silva, Joao Santana ^[6] ; Zamboni, Dario Simoes ^[3] ; Campanelli, Ana Paula ^[1]

Affiliation

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci Microbiol & Immunol, Bauru, SP - Brazil

^[2] Univ Sao Paulo, Bauru Sch Dent, Dept Stomatol Oral Pathol, Bauru, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell Biol, BR-14049 Ribeirao Preto, SP - Brazil

^[4] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI - USA

^[5] Consejo Nacl Invest Cient & Tecn Argentina, Inst Biol & Med Expt, Lab Mecanismos Mol Carcinogenesis, Buenos Aires, DF - Argentina

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 9, n. 9 SEP 30 2014.
• Web of Science Citations: 8

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-1 beta, IL-18, Tumor Necrosis Factor (TNF)-alpha and Interferon (IFN)-gamma 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. (AU)

• FAPESP's process: 11/09664-3 - Influence of the inflamassoma on the squamous cell carcinoma development in an experimental model
• Grantee: Luisa Thomazini de Freitas
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 09/14127-7 - The role of inflammasomes in chemically induced tumor
• Grantee: Thaís Helena Gasparoto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/15331-0 - Analysis of CCR5-dependent Regulatory T cell migration: correlation with SCC development
• Grantee: Ana Paula Campanelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 11/03195-1 - The role of inflammasomes in chemically induced tumor
• Grantee: Ana Paula Campanelli
• Support Opportunities: Regular Research Grants