Immune checkpoint inhibitors highlight the importance of anticancer immunity. However, their clinical utility and safety are limited by low response rates adverse effects. We focused on progesterone (P4), a hormone produced placenta during pregnancy, because it has multiple biological activities related to immune regulation P4 reversible regulatory function distinct from that stress cortisol, w...

Immunotherapy induces durable responses in a subset of patients with cancer. High tumor mutational burden (TMB) may be a response biomarker for PD-1/PD-L1 blockade in tumors such as melanoma and non-small cell lung cancer (NSCLC). Our aim was to examine the relationship between TMB and outcome in diverse cancers treated with various immunotherapies. We reviewed data on 1,638 patients who had un...

The co-inhibitory receptor Programmed Death-1 (PD-1) curtails immune responses and prevent autoimmunity, however, tumors exploit this pathway to escape from immune destruction. The co-stimulatory receptor OX40 is upregulated on T cells following activation and increases their clonal expansion, survival and cytokine production when engaged. Although antagonistic anti-PD-1 or agonistic anti-OX40 ...

Purpose: GDC-0973 is a potent and selective MEK inhibitor. Pharmacokinetic-pharmacodynamic (PK-PD) modeling was used to relate GDC-0973 plasma and tumor concentrations, tumor pharmacodynamics (PD) and anti-tumor efficacy in order to establish pharmacokinetic endpoints and predict active doses in the clinic. Experimental Design: A PK-PD model was used to characterize GDC-0973 tumor disposition a...

Coxsackievirus A21 (CAVATAKTM) is a bio-selected oncolytic immunotherapy virus. Following intratumoral (i.t) injection, CAVATAK selectively infects ICAM-1expressing tumor cells, resulting in tumor cell lysis and a systemic immune-mediated anti-tumor response. A Phase II trial of i.t delivered CAVATAK (NCT01227551) in advanced melanoma patients has highlighted antitumor activity in both injected...

OBJECTIVE To assess associations between Parkinson disease (PD) and putatively protective factors-smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen). DESIGN Family-based case-control study. SETTING Academic medical center clinic. PARTICIPANTS A total of 356 case subjects and 317 family controls who self-reported en...

Introduction Baseline neutrophil-to-lymphocyte ratio (NLR) has been repeatedly reported as a significant prognostic factor in advanced cancer patients. We explored whether changes in NLR may predict outcome of advanced cancer patients enrolled into phase 1 trials and treated with PD-1/PD-L1 inhibitors. Patients and Methods Advanced cancer patients enrolled into phase 1 trials between Septembe...

OBJECTIVE The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to h...

Therapeutic antibodies blocking PD-1-/PD-L1 interaction have achieved remarkable clinical success in cancer. In addition to a target molecule, some isotypes of can activate complement, NK cells or phagocytes, resulting death the cell expressing antibody's target. Human anti-PD-1 therapeutics use antibody designed minimize such antibody-dependent lysis. contrast, reagents used mice are derived f...