Project description:The purpose of this study was to develop better ways of detecting prostate cancer before and after pre-operative treatment, and to test the feasibility of multi parametric magnetic resonance imaging (mpMRI) for the localization and detection of focal prostate cancer both before and after pre-operative treatment with ADT and enzalutamide. In this study, patients with intermediate and high risk prostate cancer received six months of neoadjuvant intense androgen deprivation therapy prior to radical prostatectomy. Biopsies were acquired prior to treatment. Tissue from biopsy and radical prostatectomy were subjected to sequencing and analysis for determination of features associated with response or resistance to treatment.
Project description:Androgen deprivation therapy (ADT) is a cornerstone treatment for locally advanced or metastatic prostate cancer (PCa). However, its potential effects on the tumor immune microenvironment (TIM) of PCa patients and the underlying mechanism remain largely unclear.We used RNA sequencing to reveal the effects of ADT on the PCa TIM at the transcriptome level. RNA sequencing was performed on 6 paired pre-ADT biopsy and post-ADT PCa lesions and 5 paired paracancerous benign tissues from patients receiving neoadjuvant ADT with locally advanced PCa.
Project description:Novel perioperative strategies are needed to reduce recurrence rates in patients undergoing nephrectomy for high-risk, non-metastatic clear cell renal cell carcinoma (ccRCC). We conducted a prospective, phase I trial of neoadjuvant nivolumab prior to nephrectomy in 15 evaluable patients with non-metastatic ccRCC. We leveraged tissue from that cohort to elucidate the effects of PD-1 inhibition on immune cell populations in ccRCC and correlate the evolving immune milieu with anti-PD-1 response. We found that nivolumab durably induces a pro-inflammatory state within the primary tumor, and baseline immune infiltration within the primary tumor correlates with nivolumab responsiveness. Nivolumab increases CTLA-4 expression in the primary tumor, and subsequent nephrectomy increases circulating concentrations of sPD-L1, sPD-L3 (sB7-H3), and s4-1BB. These findings form the basis to consider neoadjuvant immune checkpoint inhibition (ICI) for high-risk ccRCC while the tumor remains in situ and provide the rationale for perioperative strategies of novel ICI combinations.
Project description:Purpose: The goals of this study is to compare NGS-derived Androgen Deprivation Therapy (ADT) resistant miRNome profiling to Androgen Deprivation Therapy (ADT) sensitive miRNome profile in African American prostate cancer cells and validate by reverse transcription polymerase chain reaction (qRT–PCR) methods. Method: Mirco-RNA were isolated from different CaP cells who were sensitive and resistant to Androgen Deprivation Therapy (ADT). Total micro-RNA were subjected to miRNA-Seq. Results: We performed whole miRNA-Seq analysis through paired-end deep sequencing to systematically investigate the molecular features of different CaP cell models- RC-77-N, RC-77T/E, RCC7T/E-ADT, RCC7T/E-CD133-plus, E006AA-hT and E006AA-hT-ADT. Conclusions: Our study represents the first detailed analysis of African American ADT resistant miRNome, with biologic replicates, generated by miRNA-seq technology.
Project description:In a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with clinical malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from a subset of trial participants at baseline and month 3 (one month post-final dose). RTS,S/AS01 vaccination was associated with downregulation of B-cell and monocyte-related blood transcriptional modules (BTMs) and upregulation of T-cell related BTMs, as well as higher month 3 (vs baseline) (CSP)-specific CD4+ T-cell responses. For some RTS,S/AS01-associated BTMs, month 3 levels correlated with anti-circumsporozoite protein (CSP) IgM and inversely with anti-CSP IgG responses. There were few RTS,S/AS01-associated BTMs whose month 3 levels correlated with malaria risk. In contrast, baseline levels of dendritic cell and monocyte RTS,S/AS01-associated BTMs correlated with malaria risk. A cross-study analysis supported generalizability of these correlations to healthy, malaria-naïve adults, suggesting inflammatory monocytes may inhibit protective RTS,S/AS01-induced responses.
Project description:To investigate effects of standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy on T cell immunity, we surveyed changes in the peripheral T cell receptor repertoire. We performed bulk TCR sequencing of peripheral blood before chemotherapy (baseline), after 3 cycles (C3) and after 6 cycles (C6).