The coronavirus disease 2019 (COVID-19) virus, emerged in December 2019, has spread rapidly, with cases now confirmed in multiple countries. As of February 16, 2020, the virus has caused 70,548 infections and 1,770 deaths in mainland China and 413 infections in Japan (1). A great deal of effort has been made to find effective drugs against the virus in China (2). On February 17, 2020, the State Council of China held a news briefing indicating that chloroquine phosphate, an old drug for treatment of malaria, had demonstrated marked efficacy and acceptable safety in treating COVID-19 associated pneumonia in multicenter clinical trials conducted in China (3). In the early in vitro studies, chloroquine was found to block COVID-19 infection at low-micromolar concentration, with a half-maximal effective concentration (EC 50) of 1.13 μM and a half-cytotoxic concentration (CC 50) greater than 100 μM (4). A number of subsequent clinical trials (ChiCTR2000029939,

No abstract

No abstract

SUMMARY Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-γ, which is a critical cytokine for host immune responses. However, the role of IFN-γ signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here we demonstrate that patients identified as non-responders to anti-CTLA-4 (ipilimumab) have tumors with genomic defects in IFN-γ pathway genes. Furthermore, mice bearing melanoma tumors with knockdown of IFN-γ receptor 1 (IFNGR1) have impaired tumor rejection upon anti-CTLA-4 therapy. These data highlight that loss of the IFN-γ signaling pathway is associated with primary resistance to anti-CTLA-4 therapy. Our findings demonstrate the importance of tumor genomic data, especially IFN-γ related genes, as prognostic information for patients selected to receive treatment with immune checkpoint therapy.

The treatment of renal cell carcinoma (RCC) has changed greatly over the past 15 years. Progress in the surgical management of the primary tumor and increased understanding of the molecular biology and genomics of the disease have led to the development of new therapeutic agents. The management of the primary tumor has changed owing to the realization that clean margins around the primary lesion are sufficient to prevent local recurrence, as well as the development of more sophisticated tools and techniques that increase the safety of partial nephrectomy. The management of advanced disease has altered even more dramatically as a result of new agents that target the tumor vasculature or that attenuate the activation of intracellular oncogenic pathways. This review summarizes data from prospective randomized phase III studies on the surgical management and systemic treatment of RCC, and provides an up to date summary of the histology, genomics, staging, and prognosis of RCC. It describes the management of the primary tumor and offers an overview of systemic agents that form the mainstay of treatment for advanced disease. The review concludes with an introduction to the exciting new class of immunomodulatory agents that are currently in clinical trials and may form the basis of a new therapeutic approach for patients with advanced RCC.

Highlights d Living biobank with 80 tumor organoids was derived from treatment-naive CRC patients d Tumor organoids recapitulate histological and genetic features of original tumors d Interpatient variability in the PDO response to chemoradiation treatments d PDOs can predict locally advanced rectal cancer patient responses in the clinic

To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not demonstrated significant clinical benefit in patients with prostate cancer. To identify additional immune inhibitory pathways in the prostate tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients on a pre-surgical clinical trial. PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages. Our data suggest that VISTA is another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy.

We report the first case series of ICI-associated colitis successfully treated with fecal microbiota transplantation (FMT), with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T cells (Tregs) within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.