Developing newly combined therapeutic strategies for mature B cell lymphoma

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Cancer patients inflicted with COVID-19 are at 3.5 times the risk of requiring mechanical ventilation or ICU admission, compared to the general population. Infection of SARS-CoV-2, the causative agent of COVID-19, elicits both T and B cell responses against the virus and the successful coordination of these systems working in concert would normally lead to the control of the viral infection. However, if the immune system is compromised or defective, SARS-CoV-2 may undergo unchecked viral replication triggering cytokine storm, multiple organ failure and ultimately lethality. Conventional wisdom would suggest that fatality rate should be higher in COVID-19 infected cancer patients. While many cancer therapeutics such as chemotherapies preferentially target cancer cells, they also hurt normal cells to a degree, particularly the very cells that are involved in immune responses to infectious agents. Consequently, chemotherapies may weaken the host defense system to allow viral spreading. Other cancer treatments such as immunotherapies or CAR-T, which seek to enhance immune responses of patients to tumors, could be a double-edged sword as these treatments may also enhance the cytokine storm responses. The high mortality rate of cancer patients infected with SARS-CoV-2 begs the question whether vaccination should be prioritized. However, the effectiveness of vaccine in patients with cancer and the presence of tumors with or without anti-PD1 treatment on the development of SARS-CoV-2 immunity remains largely unknown. The goal of this administrative supplement is to investigate the effects of tumors or anti-PD-1 treatment on T and B cell responses against SARS-CoV-2 antigen in a unique syngeneic mouse tumor model we developed. We hypothesize that the presence of tumor compromises mounting of an adequate immune response to viral antigens and impedes production of neutralizing antibodies. Anti-PD1 treatment may enhance SARS-CoV-2 immunity. Two aims are proposed. In SA1, we will characterize T and B cell immune responses to SARS-CoV-2 in wild type (WT) and tumor-bearing mice. In SA2, we will determine the effect of anti-PD1 treatment on T and B cell immune responses to SARSCoV-2 in WT or tumor-bearing mice. The result may provide novel insights into the observed high mortality rate of SARS-CoV-2 inflicted cancer patients, and inform the vaccination strategy for cancer patients.