Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy. Academic Article uri icon

Overview

abstract

  • Clear cell renal cell carcinomas (ccRCCs) are highly immune infiltrated, but the effect of immune heterogeneity on clinical outcome in ccRCC has not been fully characterized. Here we perform paired single-cell RNA (scRNA) and T cell receptor (TCR) sequencing of 167,283 cells from multiple tumor regions, lymph node, normal kidney, and peripheral blood of two immune checkpoint blockade (ICB)-naïve and four ICB-treated patients to map the ccRCC immune landscape. We detect extensive heterogeneity within and between patients, with enrichment of CD8A+ tissue-resident T cells in a patient responsive to ICB and tumor-associated macrophages (TAMs) in a resistant patient. A TCR trajectory framework suggests distinct T cell differentiation pathways between patients responding and resistant to ICB. Finally, scRNA-derived signatures of tissue-resident T cells and TAMs are associated with response to ICB and targeted therapies across multiple independent cohorts. Our study establishes a multimodal interrogation of the cellular programs underlying therapeutic efficacy in ccRCC.

authors

publication date

  • April 15, 2021

Research

keywords

  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Lymphocyte Activation
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC8268947

Scopus Document Identifier

  • 85104966318

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2021.03.007

PubMed ID

  • 33861994

Additional Document Info

volume

  • 39

issue

  • 5