Immune-checkpoint inhibitors from cancer to COVID­19: A promising avenue for the treatment of patients with COVID­19 (Review).

The severe acute respiratory syndrome associated coronavirus­2 (SARS­CoV­2) poses a threat to human life worldwide. Since early March, 2020, coronavirus disease 2019 (COVID­19), characterized by an acute and often severe form of pneumonia, has been declared a pandemic. This has led to a boom in biomedical research studies at all stages of the pipeline, from the in vitro to the clinical phase. In line with this global effort, known drugs, currently used for the treatment of other pathologies, including antivirals, immunomodulating compounds and antibodies, are currently used off­label for the treatment of COVID­19, in association with the supportive standard care. Yet, no effective treatments have been identified. A new hope stems from medical oncology and relies on the use of immune­checkpoint inhibitors (ICIs). In particular, amongst the ICIs, antibodies able to block the programmed death­1 (PD­1)/PD ligand-1 (PD­L1) pathway have revealed a hidden potential. In fact, patients with severe and critical COVID­19, even prior to the appearance of acute respiratory distress syndrome, exhibit lymphocytopenia and suffer from T­cell exhaustion, which may lead to viral sepsis and an increased mortality rate. It has been observed that cancer patients, who usually are immunocompromised, may restore their anti­tumoral immune response when treated with ICIs. Moreover, viral-infected mice and humans, exhibit a T­cell exhaustion, which is also observed following SARS­CoV­2 infection. Importantly, when treated with anti­PD­1 and anti­PD­L1 antibodies, they restore their T­cell competence and efficiently counteract the viral infection. Based on these observations, four clinical trials are currently open, to examine the efficacy of anti­PD­1 antibody administration to both cancer and non­cancer individuals affected by COVID­19. The results may prove the hypothesis that restoring exhausted T­cells may be a winning strategy to beat SARS­CoV­2 infection.

Cancer Management during COVID-19 Pandemic: Is Immune Checkpoint Inhibitors-Based Immunotherapy Harmful or Beneficial?

The coronavirus disease 2019 (COVID-19) is currently representing a global health threat especially for fragile individuals, such as cancer patients. It was demonstrated that cancer patients have an increased risk of developing a worse symptomatology upon severe acute respiratory syndrome associated coronavirus-2 (SARS-CoV-2) infection, often leading to hospitalization and intensive care. The consequences of this pandemic for oncology are really heavy, as the entire healthcare system got reorganized. Both oncologists and cancer patients are experiencing rescheduling of treatments and disruptions of appointments with a concurrent surge of fear and stress. In this review all the up-to-date findings, concerning the association between COVID-19 and cancer, are reported. A remaining very debated question regards the use of an innovative class of anti-cancer molecules, the immune checkpoint inhibitors (ICIs), given their modulating effects on the immune system. For that reason, administration of ICIs to cancer patients represents a question mark during this pandemic, as its correlation with COVID-19-associated risks is still under investigation. Based on the mechanisms of action of ICIs and the current evidence, we suggest that ICIs not only can be safely administered to cancer patients, but they might even be beneficial in COVID-19-positive cancer patients, by exerting an immune-stimulating action.