Lung cancer immune cells exhibit inhibited inflammasome response

Lung cancer cells continuously interact with local and systemic immune cells, thus guiding tumor evasion, tissue injury and progressive cellular pathology. Moreover, a number of studies provide evidence that infectious products are associated with lung cancer tissue recovered from a significant number of patients, so we aimed to investigate the inducibility of the NLRP3 pathway in Bronchoalveolar Lavage macrophages and peripheral blood leukocytes from patients with primary lung cancer compared to healthy individuals. The presence or absence of mediators (NLRP3, Caspase-1) and outcomes (TNF-α, IL-1β, IL-6, IL-18) after inflammasome activation via LPS plus ATP were evaluated with RT-PCR, Western Blotting and ELISA kits. IL-1β protein production is severely inhibited in lung cancer macrophages and leukocytes compared to controls, while only macrophages showed a reversible inducibility of NLRP3 inflammasome. In addition, TNFα secretion after inflammasome activation is significantly prohibited in lung cancer samples, while IL-1β secretion profile in lung cancer suggest reversibility of NLRP3 induction in blood samples but not in lung macrophages. IL-6 remains the only reversible outcome, in both BAL and blood, in lung cancer compared to controls. IL-6 pronounced systemic inducibility leads to the possibility that systemic inflammation in lung cancer could be mediated via NLRP3 inflammasome, while immunosuppression or immunodepletion could explain TNFα profiling in the activation of NLRP3 inflammasome.