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.