Abstract
Lung cancer (LC) remains the leading cause of cancer-related mortality. The interaction of cancer cells with their microenvironment, results in tumor escape or elimination. Alveolar macrophages (AMs) play a significant role in lung immunoregulation, however their role in LC has been outshined by the study of tumor associated macrophages. Inflammasomes are key components of innate immune responses and can exert either tumor-suppressive or oncogenic functions, while their role in lung cancer is largely unknown. We thus investigated the NLRP3 pathway in Bronchoalveolar Lavage derived alveolar macrophages and peripheral blood leukocytes from patients with primary lung cancer and healthy individuals. IL-1β and IL-18 secretion was significantly higher in unstimulated peripheral blood leukocytes from LC patients, while IL-1β secretion could be further increased upon NLRP3 stimulation. In contrast, in LC AMs, we observed a different profile of IL-1β secretion, characterized mainly by the impairment of IL-1β production in NLRP3 stimulated cells. AMs also exhibited an impaired TLR4/LPS pathway as shown by the reduced induction of IL-6 and TNF-α. Our results support the hypothesis of tumour induced immunosuppression in the lung microenvironment and may provide novel targets for cancer immunotherapy.
Highlights
Lung cancer remains the leading cause in cancer-related mortality in both males and females
We aimed to investigate an IL-1β specific pathway, the NLRP3 inflammasome, in lung cancer peripheral blood leukocytes and alveolar macrophages obtained from bronchoalveolar lavage and to characterize this inflammatory process in primary lung cancer in the periphery and locally in the lungs
We aimed to investigate a central innate immune response pathway, the NLRP3 inflammasome, in lung cancer PBMCs and Alveolar macrophages (AMs), in order to gain insight on inflammatory processes related to Lung cancer (LC)
Summary
Lung cancer remains the leading cause in cancer-related mortality in both males and females. 85% of lung tumours are non-small cell lung cancer (NSCLC), including adenocarcinoma, squamous cell carcinoma and large cell carcinoma [1]. The majority of lung cancer patients are smokers, only a minority among smokers will develop this disease, strongly suggesting that additional environmental determinants including infections, in a background of genetic susceptibility, drive disease initiation and progression[2]. The crosstalk between inflammation and tumorigenesis is a field of active research and cell-autonomous aberrations are considered the initiators of cancer, chronic inflammation has been shown to promote cancer initiation and progression [3].
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