title: Targeting inflammasome/IL-1 pathways for cancer immunotherapy.
abstract: The inflammatory microenvironment has been shown to play important roles in various stages of tumor development including initiation, growth, and metastasis. The inflammasome is a critical innate immune pathway for the production of active IL-1β, a potent inflammatory cytokine. Although inflammasomes are essential for host defense against pathogens and contribute to autoimmune diseases, their role in tumor progression remains controversial. Here, our results demonstrate that the inflammasome and IL-1β pathway promoted tumor growth and metastasis in animal and human breast cancer models. We found that tumor progression was associated with the activation of inflammasome and elevated levels of IL-1β at primary and metastatic sites. Mice deficient for inflammasome components exhibited significantly reduced tumor growth and lung metastasis. Furthermore, inflammasome activation promoted the infiltration of myeloid cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) into tumor microenvironments. Importantly, blocking IL-1R with IL-1R antagonist (IL-Ra) inhibited tumor growth and metastasis accompanied by decreased myeloid cell accumulation. Our results suggest that targeting the inflammasome/IL-1 pathway in tumor microenvironments may provide a novel approach for the treatment of cancer.
authors: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, United States of America.|Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina 29425-5040. United States of America.
authors: Beichu
authors: B
authors: Guo
authors: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, United States of America.
authors: Shunjun
authors: S
authors: Fu
authors: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, United States of America.
authors: Jinyu
authors: J
authors: Zhang
authors: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, United States of America.|Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina 29425-5040. United States of America.
authors: Bei
authors: B
authors: Liu
authors: Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, United States of America.|Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina 29425-5040. United States of America.
authors: Zihai
authors: Z
authors: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007167:Immunotherapy; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000172:deficiency / Q000235:genetics; D000070576:NLR Proteins / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C492716:Nlrp3 protein, mouse; D017472:Receptors, Interleukin-1; D020170:Caspase 1