SARS-COV-2 infection and lung tumor microenvironment

Abstract

Coronavirus Disease 2019 (COVID-19) is an acute respiratory syndrome, reported at the end of 2019 in China originally and immediately spread affecting over ten million world population to date. This pandemic is more lethal for the older population and those who previously suffered from other ailments such as cardiovascular diseases, respiratory disorders, and other immune system affecting abnormalities including cancers. Lung cancer is an important comorbidity of COVID-19. In this review, we emphasized the impact of lung tumor microenvironment (TME) on the possibility of enhanced severity of infection caused by the SARS-Co-V2. The compromised lung TME is further susceptible to the attack of viruses. The lung cells are also abundant in the virus entry receptors. Several SARS-Co-V2 proteins can modulate the lung TME by disrupting the fragile immune mechanisms contributing to cytokine storming and cellular metabolic variations. We also discussed the impact of medication used for lung cancer in the scenario of this infection. Since other respiratory infections can be a risk factor for lung cancer, COVID-19 recovered patients should be monitored for tumor development, especially if there is genetic susceptibility or it involves exposure to other risk factors.

Keywords: Covid-19; Cytokines; Lung cancer; Risk factors; Tumor microenvironment.

Fig. 1

Tumor microenvironment (TME) in lung cancer. The TME components support the tumor growth and secrete signals and initiate cascades that facilitate the proliferation, growth, migration, invasion, and stabilization of tumor cells. They also suppress immune responses and confer drug resistance. IGF2 (insulin-like growth factor-2), CXCL1 (C-X-C Motif Chemokine Ligand 1), STAT (Signal Transducer And Activator Of Transcription), TGF-β (Transforming Growth Factor Beta), IL-6 (Interleukin-6), FASL (Fas Ligand), PDL1/L2 (Programmed cell death protein ligand 1 and 2), EGF (Epidermal growth factor), MMP14 (Matrix metalloproteinase 14), HIF1A1α (Hypoxia-inducible factor 1A1alpha), HMMR (Hyaluronan mediated motility receptor), mTOR (mammalian target of rapamycin), IL-1β (Interleukin-1beta), sRAGE (soluble Advanced Glycosylation End-Product Specific Receptor), CXCR2 (C-X-C Motif Chemokine Receptor 2), VEGF (Vascular endothelial growth factor), PIGF (Placental growth factor), IFN-γ (Interferon-gamma), TNF-α (Tumor necrosis factor-alpha)

Fig. 2

Structure of SARS-CoV-2. a A virus particle showing structural proteins and single-stranded RNA genome; b A schematic figure of viral 29.9 kb genome showing 5′UTR, location of the polyprotein, 04 structural proteins, 16 non-structural proteins, 09 accessory proteins, and 3′UTR

Fig. 3

SARS-CoV-2 binds to ACE2 receptors on the host cell surface and gains entry. Once inside it can start its life cycle by using components of the host cell. The virus makes multiple copies that leave by exocytosis to infect other cells

Fig. 4

Molecular events predicting the development of lung tumor in response to SARS-CoV-2 infection. ALI (acute lung injury), ARDS (acute respiratory distress syndrome), IFN (Interferons), TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin-6), IL-1 (interleukin-1), MIP-1 (macrophage inflammatory protein-1), IP-10 (interferon gamma-induced protein 10), STAT (signal transducers and activators of transcription), MAPK (mitogen-activated protein kinase), NF-κB (nuclear factor kappa B), ERK1/2 (extracellular receptor kinase), EGF (epidermal growth factor), PI3-AKT (phosphatidylinositol 3 kinase- protein kinase B)