HCA Data Explorer

Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment.

Access Granted
Updated August 2, 2024

Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We profiled 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph nodes, using single-cell RNA-seq. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous phenotypic expansions specific to the tumor microenvironment. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer. Our results have important implications for characterizing tumor-infiltrating immune cells.

Dana Pe'erProgram for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: peerd@mskcc.org.
Elham Azizi1
Ambrose J Carr2
George Plitas3
Andrew E Cornish1
Catherine Konopacki4
Sandhya Prabhakaran1
Juozas Nainys5
Kenmin Wu6
Vaidotas Kiseliovas7
Manu Setty1
Kristy Choi8
Rachel M Fromme9
Phuong Dao1
Peter T McKenney10
Ruby C Wasti11
Krishna Kadaveru11
Linas Mazutis1
Alexander Y Rudensky12
Dana Pe'er (Principal Investigator)13
1Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
2Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Biological Sciences, Columbia University, New York, NY, USA.
3Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
4Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
5Department of Biological Sciences, Columbia University, New York, NY, USA; Sector of Microtechnologies, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
6Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
7Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Sector of Microtechnologies, Institute of Biotechnology, Vilnius University, Vilnius, Lithuania.
8Department of Biological Sciences, Columbia University, New York, NY, USA.
9Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
10Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
11Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
12Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Ludwig Center at Memorial Sloan Kettering Cancer Center, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: rudenska@mskcc.org.
13Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: peerd@mskcc.org.
Ray Stefancsik

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/7c75f07c-608d-4c4a-a1b7-b13d11c0ad31
None
GEO Series Accessions:INSDC Project Accessions:
SRP148597, SRP148594
INSDC Study Accessions:

Analysis Portals

None

Project Label

GSE114727_BreastTumorMicroenvironment

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

3 anatomical entities

Organ Part

3 organ parts

Selected Cell Types

4 cell types

Disease Status (Specimen)

3 disease statuses

Disease Status (Donor)

2 disease statuses

Development Stage

human adult stage

Library Construction Method

3 library construction methods

Nucleic Acid Source

single cell

Paired End

true

Analysis Protocol

data_analysis_protocols

File Format

3 file formats

Cell Count Estimate

72.0k

Donor Count

11
fastq.gz406 file(s)tar1 file(s)xlsx1 file(s)