Immune Regulation of COVID-19 Infection in Cancer and Autoimmunity

Project 3: Title: Regulation of SARS CoV-2 immunity in cancer patients Project leaders: Madhav Dhodapkar and Rafi Ahmed Project Summary: Patients with cancer are at increased risk of morbidity and mortality relating to SARS CoV-2 infection. However the immunologic underpinnings of wide variance in COVID-19 disease course in cancer patients are unknown. In addition to underlying cancer associated immune paresis, therapies used to treat cancer can further increase the risk of COVID related pathology. In this proposal, we have assembled a multidisciplinary team to tackle these questions. These studies build directly on our prior expertise and experience in studying immunity in viral infections and cancer. We will focus in particular on patients with B/plasma cell tumors treated with B/plasma cell depleting therapies and those with lung cancer treated with immune checkpoint blockade. Studies in aim 1 will evaluate the impact of therapy-related immune paresis on protective immunity to SARS CoV-2 and viral clearance in patients with B/plasma cell malignancies. Studies in aim 2 will evaluate anti-viral immunity and immunopathology in patients with lung cancer receiving immune checkpoint blockade. Studies in aim 3 will evaluate immunologic responses to SARS CoV-2 vaccines in patients with B/plasma cell tumors and lung cancer once they are approved and administered as a part of standard care. These studies will not only provide basic insights into protective immunity to SARS CoV-2, but also provide essential information for optimal care of these patients in the face of concurrent SARS CoV-2 infection.