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Series GSE246613 Query DataSets for GSE246613
Status Public on Jan 01, 2024
Title Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Cancer immunotherapy trials have produced encouraging results, but resistance remains a problem necessitating strategies to identify patients that benefit from immunotherapy alone or who require additional combinations like chemotherapy or radiotherapy. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken before and after one cycle of pembrolizumab and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high MHC expression, evidence of tertiary lymphoid structures and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response after the combination therapy, which is characterized by cytotoxic T cell and antigen presenting myeloid cell interactions and is mirrored in murine breast tumors only after radiation.
 
Overall design From November 2017 through June 2021, we enrolled 50 patients in our phase Ib/II trial entitled “Preoperative Combination of Pembrolizumab and Radiation Therapy in Patients with Operable Breast Cancer”03366844, clinicaltrials.gov). Patients with tumors greater than 2 cm with any nodal status as determined by imaging without metastatic disease were eligible for the trial. Patients received pembrolizumab at a dose of 200 mg, administered intravenously, on Day 1 and 21 and received three daily fractions of 8 Gray (Gy) stereotactic radiation to the breast tumor only between Day 21 and 28. Biopsies were taken prior to each treatment and patients were consented to analysis of the biopsies which included, but were not limited to, sequencing and immunohistochemistry. We utilized the E0771 orthotopic murine model of TNBC and performed a four-arm study consisting of control IgG treatment, anti-PD1 treatment, control IgG + radiation therapy, or anti-PD1 + radiation therapy. We then performed single-cell RNA-sequencing on CD45-positive cells isolated from tumors (n=2, with 2 mice pooled per replicate) from each of the arms.
 
Contributor(s) Knott SR, Shiao SL, Gouin III KH, Shah AB
Citation(s) 38194915
BioProject PRJNA1032700
Submission date Oct 31, 2023
Last update date Mar 12, 2024
Contact name Simon Knott
E-mail(s) simon.knott@cshs.org
Organization name Cedars Sinai
Department BFG
Street address 8687 Melrose Ave
City West Hollywood
State/province California
ZIP/Postal code 90069
Country USA
 
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (266)
GSM7872698 h01A_P
GSM7872699 h01A_TCR
GSM7872700 h01C_P

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE246613_PembroRT_immune_R100_final.h5ad.gz 1.0 Gb (ftp)(http) H5AD
GSE246613_PembroRT_non_immune_cells.h5ad.gz 1.4 Gb (ftp)(http) H5AD
GSE246613_TCRtable_annotation_expansion_detection.csv.gz 14.9 Mb (ftp)(http) CSV
GSE246613_combined_RTPDv4_scvi_celltypist.h5ad.gz 376.6 Mb (ftp)(http) H5AD
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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