key: cord-0978905-b5pebtwm authors: Cafarotti, Stefano title: SARS-COV2 INFECTION AND LUNG CANCER PATIENTS: the potential role of IL17 target therapy date: 2020-04-27 journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer DOI: 10.1016/j.jtho.2020.04.015 sha: d2c74e5d2586d599f782f51c887d6e39704793cb doc_id: 978905 cord_uid: b5pebtwm Abstract The coronavirus disease 2019 (Covid-19) outbreak is evolving rapidly worldwide. The Lung is the target organ of the primary infection and patient whit lung cancer seems to have a poor prognosis. This is the first reported investigation on a possible role of IL 17 target therapy in Lung Cancer patients with concomitant Sars-CoV2 infection. organ damage mediated by viruses through the IL-17 pathway. The role of IL-17 does not seem to be confined to these mechanisms, in fact in addition to mediating the cytokine storm (at the basis of lung damage) and inhibiting the apoptosis of infected cells (at the basis of viral persistence) it also seems to have the ability to increase the replication of some viruses by actually increasing their virulence (3) . It has also been demonstrated on an experimental model that viral persistence, by generating a continuous increase in IL-17, produces ARDS (Acute distress respiratory Syndrome) (4), just as it happens in SARS-CoV-2 infection. The increasing level of IL-17 could also be related to the hypercoagulation status in COVID 19 patient (5). By investigating the risk factors most related to the poor prognosis of COVID-19, it turns out that the IL-17 pathway is always altered in these cases. In fact, with advancing age the inflammatory response to viruses is altered with an excessive increase in the production of IL-17 (6); the same thing happens in asthma (7), smokers (8), diabetics (9), heart patients (10-11) and in male gender (12) . There are some emerging evidences in support of the IL-17 role in Sars-Cov2 pathogenesis, such us the first anatomopathological lung analysis (with high number of TH17 lymphocytes into the alveolar space) (13) , and two recent pubblications (14)(15) that reviewed the immune respons in patient whit SARS-CoV2 infection. It is well know the role of IL-17 in Lung Cancer (16) , indeed IL-17 could induce VEGF secretion in cancer cell lines (17) . This effect was dependent of the STAT3-Gα-Interacting Vesicle-associated protein (GIV) pathway and was abolished when cells where exposed to small interfering RNA (siRNA) (18) . In patients, was observed that those with increased levels of serum IL-17 had a poorer survival and an enhanced angiogenesis compared to healthy control (19) . To comfort that, exposure of three different NSCLC cell lines to IL-17 has also been reported to increase neoangiogenesis and to promote in vivo tumor growth in SCID mice through a CXCR-2-dependent mechanism. IL-17 up-regulated several pro-angiogenic CXC chemokines including CXCL1, CXCL5, CXCL6 and CXCL8. Inhibition of IL-17 with monoclonal antibodies abolished this up-regulation and could be potentially useful in those patient whit COVID-19 when other systemic therapy are excluded due to the Sars-Cov2 infection. The anti IL17 use is well consolidated, it is approved in psoriatic arthritis. The anti-IL17 antibodies have already demonstrated a therapeutic role not only in differ cancer type (16) but also in the treatment of lung infection with H1N1 virus (19) , in ARDS (4) (20) and in pulmonary fibrosis (21) . Based on this analysis, and according to the specific context of global pandemic, with a high social impact and without specific validated treatments, there seem to be theoretic elements to test in a clinical trial the potential utility of the use of anti-IL-17 antibodies in case of COVID-19 in Lung cancer patients. If a trial will be able to demonstrate that IL17 target therapy can determine both the control of tumor disease and resolution of Sars-Cov2 infection, it could than also be applied to other tumors in which IL17 play a role (15) . A trial in cancer free patients could be also an opportunity before a specific COVID-19 treatment. 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