CD8 T cells may fight COVID-19 infection in hematological cancer when B cells, antibodies wane

Reuters Health - 08/06/2021 - In patients with blood cancers who contract COVID-19, CD8 T cells may fight the infection when B cells and antibodies are depleted by drug treatment, researchers suggest.

"We were very concerned about our patients being treated with anti-CD20 during COVID-19 and we were encouraged to see that there were many patients who recovered, despite having no B cells or antibody responses," Dr. Alexander Huang of the Perelman School of Medicine at the University of Pennsylvania told Reuters Health by email. "This suggested that other cell types could possibly compensate, even if we depleted B cells for therapeutic reasons."

To investigate, Dr. Huang and colleagues conducted a series of analyses, reported in Nature Medicine. First they did an observational study of 100 cancer patients (median age, 68; 48% women; 54%, Black) hospitalized with COVID-19.

After adjustment for ECOG performance, disease status and other relevant factors, hematologic cancer was found to be "strongly associated" with mortality compared with solid cancer (odds ratio, 3.3), and was in fact an independent risk factor for death.

In two additional cohorts, flow cytometric and serologic analyses showed that patients with solid cancer and those without cancer had a similar immune phenotype during acute COVID-19 infection, whereas patients with hematologic cancer had impaired B cell and SARS-CoV-2-specific antibody responses.

High-dimensional analyses showed that hematologic cancer patients with depleted T cell responses had the highest mortality, regardless of the presence of B cell responses. By contrast, those with a greater number of CD8 T cells had improved survival, even after anti-CD20 therapy.

Further, 77% of hematologic cancer patients had detectable SARS-CoV-2-specific T cell responses, suggesting that CD8 T cells might influence COVID-19 recovery when humoral immunity is deficient, and that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.

Interestingly, the compensatory role of T cells occurred only in patients with hematologic, but not solid, malignancies.

The authors state, "CD8 T cells likely play an important role in the setting of quantitative and qualitative B cell dysfunction in patients with lymphoma, multiple myeloma and leukemia undergoing alphaCD20 therapy, chemotherapy or Bruton tyrosine kinase inhibition."

Dr. Huang added, "Cancer patients, even hematologic cancer patients should be vaccinated - even if they don't develop antibody responses. T cell immunity could be important."

Right now, he said, "We're trying to understand what happens to antibody and T cell immunity after hematologic cancer patients recover from COVID-19 - how protected they are, despite having compromised B cells."

Dr. Ryotaro Nakamura, a clinical professor in the division of Leukemia, and director, Center for Stem Cell Transplantation at City of Hope in Duarte, California, called the study "very helpful" from a clinical standpoint.

Nonetheless, he told Reuters Health by email, "A relatively small number of blood cancer patients were studied. The data need to be interpreted with caution given the heterogeneity and various treatments for blood cancers."

SOURCE: https://go.nature.com/2STOVWf Nature Medicine, online May 20, 2021.

By Marilynn Larkin



Posted on 8 June 202122 June 2021