Tumor characteristics in immunosuppressed and renal dysfunction populations.

Purpose: Renal transplantation and end-stage renal disease are increasingly common. Renal dysfunction and immunosuppression are two risk factors in the development of renal cell carcinoma. Carcinomas in these patients are thought to be more indolent, however data are limited and mixed.

Neoadjuvant androgen deprivation therapy with or without Fc-enhanced non-fucosylated anti-CTLA-4 (BMS-986218) in high risk localized prostate cancer: a randomized phase 1 trial.

Men with high-risk localized prostate cancer exhibit high rates of post-surgical recurrence. In these patients, androgen deprivation therapy (ADT) is immunomodulatory, however increased infiltration of regulatory T cells (Tregs) may limit the antitumor immune effects of ADT. We designed a neoadjuvant clinical trial to test whether BMS-986218 - a next-generation non-fucosylated anti-CTLA-4 antibody engineered for enhanced antibody-dependent cellular cytotoxicity or phagocytosis (ADCC/P) - depletes intratumoral Tregs and augments the response to ADT.

The role of social-evaluative threat for cortisol profiles in response to psychosocial stress: A person-centered approach.

Heterogeneity in individuals' physiological stress responses is central to theories linking stress with vulnerability to disease. Although multiple cortisol profiles have been reported in response to acute psychological stress, most prior work focuses on a single, average pattern and relative deviations from it, such as greater or lesser response peaks or reactivity. The present aims were to identify cortisol stress response trajectory classes using a data-driven approach and test whether social-evaluative threat (SET), a reliable elicitor of cortisol, predicted a greater likelihood of membership in the more reactive profiles.

Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer.

When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy.

A Transcriptome-Based Precision Oncology Platform for Patient-Therapy Alignment in a Diverse Set of Treatment-Resistant Malignancies.

Unlabelled: Predicting in vivo response to antineoplastics remains an elusive challenge. We performed a first-of-kind evaluation of two transcriptome-based precision cancer medicine methodologies to predict tumor sensitivity to a comprehensive repertoire of clinically relevant oncology drugs, whose mechanism of action we experimentally assessed in cognate cell lines. We enrolled patients with histologically distinct, poor-prognosis malignancies who had progressed on multiple therapies, and developed low-passage, patient-derived xenograft models that were used to validate 35 patient-specific drug predictions.