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K. are supported by the Ligue contre le Cancer (équipe labellisée); Agence Nationale de la Recherche (ANR)–Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Le Cancer du Sein, Parlons-en!”; Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; Fondation Carrefour; High-end Foreign Expert Program in China (GDW20171100085), Institut National du Cancer (INCa); INSERM (HTE); Institut Universitaire de France; LeDucq Foundation; LabEx Immuno-Oncology (ANR-18-IDEX-0001); RHU Torino Lumière; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). 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The immune response to SARS-CoV-2 is known to involve all the components of the immune system that together appear responsible for viral … Only late (day 7) parameters, such as the rise in transitional plasmablasts usually found in responders, were not influenced by age56. 6, 1108–1110 (2020). Cancer Immunol. Lancet 395, 1033–1034 (2020). J. 5, 33 (2020). Nat. For instance, the study from the Veneto region of Italy reported a higher percentage of COVID-19-related hospitalizations (56% versus 34%) and deaths (14% versus 4%) among patients with a history of cancer than among those without such a history16. Transforming growth factor-β and peripheral regulatory cells are negatively correlated with the overall survival of hepatocellular carcinoma. Med. Ann. Kirsch, D. G., Diehn, M., Cucinotta, F. A. Cell 181, 271–280.e8 (2020). 9, 601–604 (2020). Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. 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Here we discuss why those with cancer are at higher risk of severe COVID-19, describe immune responses that confer protective or adverse reactions to this disease and indicate which antineoplastic therapies may either increase COVID-19 vulnerability or have a dual therapeutic effect on cancer and COVID-19. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Survival study of hospitalised patients with concurrent COVID-19 and haematological malignancies. 281, 133–139 (2019). Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Similarly, morbidly obese individuals (body mass index ≥40 kg/m2) with T2D are more likely to become infected by SARS-CoV-2 and are at a higher risk of complications and death from COVID-1966. Biophys. J. Infect. 90, 8924–8933 (2016). Shaw, M. M., Gürr, W. K., Watts, P. A., Littler, E. & Field, H. J. Ganciclovir and penciclovir, but not acyclovir, induce apoptosis in herpes simplex virus thymidine kinase-transformed baby hamster kidney cells. Radiother. Immunosenescence and inflammaging, which are also promoted by aging and obesity, result in declining functions of the innate and adaptive immune systems, exacerbating overt inflammation and cancer dissemination and also increasing vulnerability to SARS-CoV-2 infection and risk of severe COVID-19. Allison Logan, S., Brissenden, A. J., Szewczuk, M. R. & Neufeld, R. J. Combinatorial and sequential delivery of gemcitabine and oseltamivir phosphate from implantable poly(d,l-lactic-co-glycolic acid) cylinders disables human pancreatic cancer cell survival. Race and ethnicity are also associated with COVID-19 risk, with Black and Hispanic people being disproportionately affected compared with white people9. A retrospective single‐center analysis of 34 patients with hematological malignancies who developed COVID‐19 during follow‐up was conducted in Spain, reporting 11 deaths that could have been predicted by ECOG (Eastern Cooperative Oncology Group) status at disease onset24. Given that IL-6 is therapeutically targeted by tocilizumab in the context of COVID-19 to reduce morbidity and mortality related to COVID-19 cytokine release syndrome45, it is conceivable—although it remains to be demonstrated—that inflammaging favors the development of severe SARS-CoV-2 infection. Totura, A. L. et al. SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19. 1). Chemother. For example, inhibitors of translation elongation factors may have such a dual activity because both cancer cells and coronaviruses rely on cap-dependent mRNA translation. 4, 905–913 (2014). 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Severe COVID-19 is also marked by dysfunction in the immune cells that are first at the scene of a viral infection, including myeloid cells such as neutrophils and monocytes. Oncol. Oncol. Maksimovic-Ivanic, D. et al. Oncoimmunology 9, 1760686 (2020). Immunological mechanisms contributing to the double burden of diabetes and intracellular bacterial infections. Vascular endothelial growth factor blockade promotes the transition from compensatory cardiac hypertrophy to failure in response to pressure overload. Cancer Commun. Human thymopoiesis is influenced by a common genetic variant within the TCRA–TCRD locus. Interestingly, individuals with T2D were also at increased risk for SARS and MERS67. Immune phenotyping based on the neutrophil-to-lymphocyte ratio and IgG level predicts disease severity and outcome for patients with COVID-19. all rights reserved. Dewan, M. Z. et al. Oncologist 11, 1121–1131 (2006). te Poele, R. H., Okorokov, A. L., Jardine, L., Cummings, J. Immunol. People with weakened immune systems are at higher risk of getting severely sick from SARS-CoV-2, the virus that causes COVID-19. Through their participation in immunosurveillance, lymphocytes control the incidence, progression and therapeutic response of cancers78. Perros, F. et al. Clin. In this section we discuss some of these therapeutic agents. Antiviral Res. Res. 38, 3493–3500 (2018). PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival. Clin. Ripani, P. et al. Oncol. Cancer Discov. Li, F. et al. Robilotti, E. V. et al. Carcinogenesis is also associated with defective antigen presentation and DC functions, including DC loss and migration defects51,52, which paves the way toward decreased antiviral T cell responses. Br. Cochrane Database Syst. Sci. Pharmacol. Medicine (Baltimore) 98, e17252 (2019). Univariate analyses identified age >65, current or former smoking, presence of any comorbidities and chemotherapy as being associated with increased risk of death. 39, 1088–1095 (2015). Despite the absence of a causative link between the manifestation of a cytokine release syndrome and COVID-19 severity, investigators have attempted to interfere with this inflammatory cascade. Nat. A study reporting the clinical outcome of COVID-19 in 102 patients with lung cancer showed that the course of SARS-CoV-2 infection in these individuals was longer and more severe than that reported in the general US population21. Lee, L. Y. et al. Metab. Rep. 42, 1248–1256 (2019). The ACE2 receptor is highly expressed in lung alveolar type 2 cells, but is also present on endothelial and smooth muscle cells in various organs, including the heart, liver, kidney and digestive tract8.

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