当前位置： SCI文献检索 > BREAST CANCER RESEARCH AND TREATMENT期刊下所有文献 > Serial single-cell profiling analysis of metastatic TNBC during Nab-paclitaxel and pembrolizumab treatment.

Serial single-cell profiling analysis of metastatic TNBC during Nab-paclitaxel and pembrolizumab treatment.

Abstract：

PURPOSE:Immunotherapy has recently been shown to improve outcomes for advanced PD-L1-positive triple-negative breast cancer (TNBC) in the Impassion130 trial, leading to FDA approval of the first immune checkpoint inhibitor in combination with taxane chemotherapy. To further develop predictive biomarkers and improve therapeutic efficacy of the combination, interrogation of the tumor immune microenvironment before therapy as well as during each component of treatment is crucial. Here we use single-cell RNA sequencing (scRNA-seq) on tumor biopsies to assess immune cell changes from two patients with advanced TNBC treated in a prospective trial at predefined serial time points, before treatment, on taxane chemotherapy and on chemo-immunotherapy. METHODS:Both patients (one responder and one progressor) received the trial therapy, in cycle 1 nab-paclitaxel given as single agent, in cycle 2 nab-paclitaxel in combination with pembrolizumab. Tumor core biopsies were obtained at baseline, 3 weeks (after cycle 1, chemotherapy alone) and 6 weeks (after cycle 2, chemo-immunotherapy). Single-cell RNA sequencing (scRNA-seq) of both cancer cells and infiltrating immune cells isolated were performed from fresh tumor core biopsy specimens by 10 × chromium sequencing. RESULTS:ScRNA-seq analysis showed significant baseline heterogeneity of tumor-infiltrating immune cell populations between the two patients as well as modulation of the tumor microenvironment by chemotherapy and immunotherapy. In the responding patient there was a population of PD-1high-expressing T cells which significantly decreased after nab-paclitaxel plus pembrolizumab treatment as well as a presence of tissue-resident memory T cells (TRM). In contrast, tumors from the patient with rapid disease progression showed a prevalent and persistent myeloid compartment. CONCLUSIONS:Our study provides a deep cellular analysis of on-treatment changes during chemo-immunotherapy for advanced TNBC, demonstrating not only feasibility of single-cell analyses on serial tumor biopsies but also the heterogeneity of TNBC and differences in on-treatment changes in responder versus progressor.

journal_name

Breast Cancer Res Treat

journal_title

Breast cancer research and treatment

authors

Deng J,Thennavan A,Shah S,Bagdatlioglu E,Klar N,Heguy A,Marier C,Meyn P,Zhang Y,Labbe K,Almonte C,Krogsgaard M,Perou CM,Wong KK,Adams S

doi

10.1007/s10549-020-05936-4

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

85-94

issue

eissn

0167-6806

issn

1573-7217

pii

10.1007/s10549-020-05936-4

journal_volume

185

pub_type

杂志文章

在线工具

Serial single-cell profiling analysis of metastatic TNBC during Nab-paclitaxel and pembrolizumab treatment.