Affiliation:
1. Systems Medicine Laboratory, National Centre for Cell Science, NCCS Complex, Ganeshkhind, SPPU Campus, Pune 411007, India
Abstract
IL-6 and IL-17 are paradoxical cytokines that progress inflammatory states in chronic diseases, including cancer. In lung cancer, their role has been elucidated to favor cancer development by modulating signaling mechanisms critical to cellular growth. The intrinsic ability of these cytokines to influence macroautophagy is yet another reason to facilitate lung cancer. Here, we employed a systems immunology approach to discover the mechanistic role of these cytokines in cancer development. In a biological system, at later stages, the activation of NFkB stimulates immunosuppressive phenotypes to achieve tolerating effects in a transformed cell. We found that the upregulation of cytokines signaled M2 macrophages to modulate tumor responses through the activation of autophagic intermediates and inflammasome mediators. This caused immune perturbations in the tumor microenvironment, which were associated with cancer inflammation. To address these inflammatory states, we performed triggered event analysis to examine whether overexpressing immune effectors or downregulating immune suppressors may have an effect on cancer reversal. Interestingly, the inhibition of immune regulators opposed the model outcome to an increased immune response. Therefore, IL6-IL17-mediated regulation of lung cancer may address tumor malignancy and potentiate the development of newer therapeutics for NSCLC.
Funder
Department of Biotechnology, Ministry of Science and Technology, Government of India
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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