Expansion of peripheral T cell clonotypes predict response in patients with small cell neuroendocrine bladder and prostate cancers treated with chemo-immunotherapy in a phase I clinical trial

To explore the impact of immunotherapy, we report a single institution, dual cohort phase Ib study (NCT 03582475) of platinum-based chemotherapy in combination with PD-1 antagonist pembrolizumab to evaluate safety and preliminary efficacy in patients with small cell bladder and small cell/neuroendocrine prostate cancers. To assess the immunologic basis for responses, single cell gene expression and T cell receptor (TCR) sequencing of serial peripheral blood samples revealed a diverse T cell repertoire with expansion of large clonotypes correlating with response. Overall design: Serial peripheral blood samples from patients with small cell bladder and small cell/neuroendocrine prostate cancers were collected. We utilized scRNA-seq and single cell immune profiling to investigate T cell repertoire related with response.

为探究免疫治疗的临床效应，本研究报道一项单中心、双队列Ib期临床试验（NCT 03582475），旨在评估铂类化疗联合PD-1拮抗剂（PD-1 antagonist）帕博利珠单抗（pembrolizumab）在小细胞膀胱癌及小细胞/神经内分泌前列腺癌患者中的安全性与初步疗效。为解析应答的免疫学基础，我们对系列外周血样本开展单细胞基因表达分析与T细胞受体（T cell receptor, TCR）测序，结果显示存在多样化的T细胞库，且大克隆型的扩增与临床应答显著相关。整体实验设计：收集小细胞膀胱癌及小细胞/神经内分泌前列腺癌患者的系列外周血样本。我们采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）与单细胞免疫分型技术，探究与临床应答相关的T细胞受体库特征。