Immunotherapy not linked to worsened complications for patients with cancer, COVID-19
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Immunotherapy did not appear to worsen complications among patients with cancer and COVID-19, according to results of a study presented at American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer.
“The COVID-19 pandemic has made a large impact throughout the world and, importantly, patients with cancer are uniquely susceptible,” Layne Weatherford, PhD, postdoctoral fellow at University of Cincinnati, said during the presentation. “Therefore, understanding COVID-19 complications and possible preventative measures is more critical than ever for these patients.”
One of the most fatal complications of COVID-19 is cytokine storm and subsequent respiratory failure, including acute respiratory distress syndrome. This also has been observed in cases of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome and influenza.
Cytokine storms are characterized by hypotension, hypoxia, fevers, coagulopathies, and increased ferritin, cytokine and chemokine levels.
Certain cancer therapies, particularly chimeric antigen receptor T-cell therapy, are associated with cytokine storms, which can be treated with interleukin-6 (IL-6) inhibitors. Immune checkpoint inhibitors also can increase cytokines associated with cytokine storm.
“PD-1 inhibitors have become a mainstay in cancer treatment, and some recent data have suggested an increased risk for severe disease if given within 90 days of COVID-19 infection,” Weatherford said. “However, other studies have shown no increased risk in patients with COVID-19.”
Weatherford and colleagues retrospectively reviewed blood samples of patients with cancer from the University of Cincinnati repository to determine whether immune checkpoint inhibitors exacerbate COVID-19 inflammatory cytokine secretion that could lead to cytokine storm in patients with cancer.
Researchers performed flow cytometry on peripheral blood mononuclear cells from patients with head and neck cancer, healthy donors and patients with COVID-19 after staining for viability and immune cell markers, including CD3, CD8, CD19 and CD45. They activated the cells overnight with low-dose interleukin-2 (IL-2), co-cultured with Cal27 or HN5 cell lines, and subjected them to various treatment conditions.
Cells from patients without COVID-19 were exposed to 25 nm SARS-CoV-2 recombinant spike protein, a virulent protein linked to cytokine storm, or control prior to drug treatments.
A preliminary flow cytometry analysis showed a COVID-19-positive patient with thyroid cancer had a higher proportion of CD8-positive cells than a COVID-19-negative patient with ovarian cancer and a healthy donor.
Recombinant SARS-CoV-2 S protein caused increased secretion of IL-6, IL-2, perforin and MIP-1b from peripheral blood mononuclear cells isolated from both healthy donors and patients with head and neck cancer.
Researchers observed that treatment with metformin, a commonly prescribed anti-diabetes drug, resulted in decreased IL-6 secretion from peripheral blood mononuclear cells isolated from a patient with COVID-19.
“Although metformin use may be limited to treat cytokine storm in hospitalized patients with COVID-19 because of potential renal dysfunction, understanding the mechanism by which metformin decreases IL-6 secretion in these patients may elucidate new targets to treat cytokine storm,” Weatherford said. “Additionally, metformin may potentially be used to prevent cytokine storm in patients with cancer and severe infections. Future work will include replicating these results, investigating other important cytokines and performing in vivo experiments.”
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Weatherford L, et al. Abstract S02-03. Presented at: AACR Virtual Meeting: COVID-19 and Cancer; July 20-22, 2020.
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