Presence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma

Immune checkpoint inhibitors (ICI) targeting the PD-1 pathway have transformed treatment of advanced renal cell carcinoma (RCC), but mechanisms underlying therapeutic response remain largely unknown. Herein, we perform transcriptomic analysis on RCC biospecimens from 102 patients enrolled in a phase II clinical trial of frontline nivolumab (NCT03117309) to investigate determinants of response to anti-PD1 monotherapy. Through bulk analysis, we identify an enrichment of genes associated with tertiary lymphoid structures (TLS) in responding patients. Using single-cell transcriptomics and external cohort validation, we identify a population of tissue-resident (ZNF683+ SLAMF7+) exhausted CD8+ T cells enriched in patients with poor clinical outcomes. Integrating these findings, we find tumors with high TLS and low tissue-resident exhausted CD8+ T cells have superior clinical outcomes with nivolumab. Altogether, these analyses contribute to a growing understanding of how the tumor microenviron..., , , # **Presence of tertiary lymphoid structures and exhausted tissue-resident T cells determines clinical response to PD-1 blockade in renal cell carcinoma**

[https://doi.org/10.5061/dryad.dv41ns28r](https://doi.org/10.5061/dryad.dv41ns28r)

## Description of the data and file structure

This dataset contains single-cell RNA sequencing (scRNA-seq) data from 19 samples from 17 renal cell carcinoma (RCC) patients, including 2 sets of paired pre- and post-treatment (aPD-1) samples. Each dataset is provided as a zip file, corresponding to one patient. The data was processed using the 10x Genomics Chromium platform and is provided in the standard sparse matrix format.

Each zip file contains the following three files:

* **barcodes.tsv** – A list of cell barcodes.
* **features.tsv** – A list of gene identifiers.
* **matrix.mtx** – A sparse matrix storing gene expression counts.

**File Naming Conventions**

The files are named using the following format:

* **260-1XXX_BL_filtered_feature_bc_ma...