COVID-19 and pediatric cancer research: potential avenues for common investigation
Our knowledge about anti-microbial and anti-cancer responses continues to evolve, as we gain understanding for their common inflammatory cellular and molecular pathways.36,37 For example, type I interferons have direct anti-viral effects, but also have key roles in anti-tumor immunity.38 Furthermore, both cancer and infectious pathogens use similar strategies to avoid immune recognition.39 Finally, chronic inflammation40 and certain viral pathogens themselves promote oncogenesis. Therefore, immune profiling of SARS-CoV-2 infection may elucidate pathways involved in oncogenesis or inflammation that could be targeted with novel or repurposed cancer or supportive therapies.41
Commonalities between anti-viral and anti-tumor responses provide “silver linings” during the COVID-19 pandemic, given they could potentially foster and provide new directions for discovering therapies for cancer and COVID-19 (Table 4 ). For example, the BCR-ABL tyrosine kinase inhibitor (TKI), imatinib, revolutionized the treatment of Philadelphia-chromosome positive (Ph+) ALL, such that allogeneic hematopoietic cell transplant in patients achieving molecular remission is no longer needed.42 Given its development as an ABL kinase inhibitor, imatinib has been shown to block coronavirus membrane fusion, inhibiting viral entry into cells.43 Similarly, the janus kinase (JAK) 1/2 inhibitor, ruxolitinib, and the blocking monoclonal IL-6 antibody, tocilizumab, may inhibit SARS-CoV-2-induced hyperinflammation19 in addition to their use in steroid-refractory graft-versus-host disease (GvHD) following allogeneic hematopoietic cell transplant44 and cytokine storm following chimeric antigen receptor (CAR) T cell therapy,45 respectively. Lastly, type I IFN, a key cytokine against viral infection and cancer,46 is being explored as a potential therapy against COVID-19.47
Community respiratory viral infections are the most common type of infection in children. Given its high prevalence, high transmissibility, and lack of established therapeutic and preventative agents, SARS-CoV-2 will likely infect the majority of adults and children. Therefore, defining potential associations of SARS-CoV-2 with future cancer risk, especially in minority populations,48,49 seems warranted. As an example, in utero cytomegalovirus (CMV) infection has been associated with subsequent ALL risk (OR=3.71, p=0.0016) most pronounced in Hispanics (OR=5.90, p=0.0006) and hypothesized to occur given the supportive role of CMV in oncogenesis through induction of chromosomal instability and immune dysregulation.50 To be clear, no specific endemic coronaviruses have been linked to cancer risk and there is no a priori biologic reason to hypothesize an association with COVID-19. But observations seem prudent, especially as the immune response to SARS-CoV-2 remains undefined at this time.
In summary, mechanistic investigation into how SARS-CoV-2 induces different immune responses in various patient populations could provide invaluable insights for the fields of infectious disease and oncology research. Likewise, clinical and epidemiology exploration defining the role of SARS-CoV-2 and the influence of COVID-19 in other disease processes might also reveal roles for the virus not previously appreciated.