T o date, hundreds of thousands of deaths have been attributed to coronavirus disease 2019 (COVID-19) 1. Millions of infections by SARS-CoV-2, the virus responsible for COVID-19, have been reported, although its full extent has yet to be determined owing to limited testing 2. Government interventions to slow viral spread have disrupted daily life and economic activity for billions of people. Strategies to ease restraints on human mobility and interaction without provoking a major resurgence of transmission and mortality will depend on accurate estimates of population levels of infection and immunity 3. Current testing for the virus largely depends on labor-intensive molecular techniques 4. Individuals with positive molecular tests represent only a small fraction of all infections, given limited deployment and the brief time window when real-time (RT)-PCR testing has the highest sensitivity 5-7. The proportion of undocumented cases in the original epidemic focus was estimated to be as high as 86% 8 , and asymptomatic infections are suspected to play a substantial role in transmission 9-14. Widely available, reliable antibody detection assays would enable more accurate estimates of SARS-CoV-2 prevalence and incidence. On February 4, 2020, the Secretary of the US Department of Health and Human Services issued an emergency use authorization (EUA) for the diagnosis of SARS-CoV-2 15 , allowing nucleic acid detection and immunoassay tests to be offered based on manufacturer-reported data without formal US Food and Drug Administration (FDA) clearance 16. In response, dozens of companies began to market laboratory-based immunoassays and point-of-care (POC) tests. Rigorous, comparative performance data are crucial to inform clinical care and public health responses.

No abstract

Inhibition of the TGF-β activating integrin, αvβ8, can dramatically enhance the effectiveness of checkpoint inhibition in multiple checkpoint resistant tumor models, but the mechanisms underlying this dramatic synergy have not been previously explored. In this study, we used single cell RNA sequencing to investigate the mechanisms of synergy between inhibition of αvβ8 and PD1 in the EMT-6 model, a checkpoint resistant model of triple negative breast cancer. Combination therapy dramatically enhanced interferon gamma (Ifnγ) expression by CD8+ and CD4+ T cells, activated interferon signaling throughout the tumor microenvironment, specifically increased Cxcl9 secretion by tumor macrophages and enhanced Gzmb expression and tumor cell killing by CD8+ T cells. The protective effects of combination therapy were inhibited by Cxcl9 blockade. These findings suggest that Ifnγ-mediated induction of Cxcl9 is an important driver of synergy between αvβ8 and checkpoint inhibition and raise the possibility that Cxcl9 might be useful as an early PD biomarker of effective combination therapy.