BIOKEY: A single-cell catalogue of the dynamic changes underlying Checkpoint Immunotherapy response in Early Breast Cancer

Checkpoint immunotherapy combined with neoadjuvant chemotherapy improves complete pathologic response in a subset of breast cancer patients. Here, we applied single-cell profiling to tumor biopsies collected before and during anti-PD1 therapy. One-third of tumors exhibited proliferative T-cells expanding along CD8+ or CD4+ lineages, which were either characterized by increased cytotoxicity and exhaustion or improved T-helper function, respectively. Lineage tracing in non-expanding tumors revealed at which point in the lineage T-cells were impaired, while gene expression modeling along these lineages revealed novel genes and underlying transcription factors involved in T-cell expansion. Interestingly, different dendritic and myeloid cell phenotypes could either stimulate or inhibit expanding T-cells, while cell-to-cell communication revealed an integrated immune context highly predictive of T-cell expansion, consisting of immune-stimulatory/-inhibitory interactions between cancer and various immune cell types. Our data yield unprecedented insights into the dynamic changes underlying checkpoint immunotherapy response in breast cancer.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

4 Datasets 21 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001006608	Single-cell RNA and VDJ sequencing of early breast cancer	Illumina NovaSeq 6000	84
EGAD00001007056	Low-coverage whole genome sequencing of 29 early breast cancer samples.	Illumina HiSeq 4000	29
EGAD00001007057	Whole-exome sequencing of 30 early breast cancer samples.	Illumina HiSeq 4000	30
EGAD00001007058	CITE-seq of early breast cancer samples.	Illumina HiSeq 4000 Illumina NovaSeq 6000	16

Publications	Citations
CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation. Hu Z, Ahmed AA, Yau C. Genome Biol 22: 2021 337	12
Bulk and Single-Cell Profiling of Breast Tumors Identifies TREM-1 as a Dominant Immune Suppressive Marker Associated With Poor Outcomes. Pullikuth AK, Routh ED, Zimmerman KD, Chifman J, Chou JW, Soike MH, Jin G, Su J, Song Q, Black MA, Print C, Bedognetti D, Howard-McNatt M, O'Neill SS, Thomas A, Langefeld CD, Sigalov AB, Lu Y, Miller LD. Front Oncol 11: 2021 734959	9
Neoantigen-specific CD4<sup>+</sup> T cells in human melanoma have diverse differentiation states and correlate with CD8<sup>+</sup> T cell, macrophage, and B cell function. Veatch JR, Lee SM, Shasha C, Singhi N, Szeto JL, Moshiri AS, Kim TS, Smythe K, Kong P, Fitzgibbon M, Jesernig B, Bhatia S, Tykodi SS, Hall ET, Byrd DR, Thompson JA, Pillarisetty VG, Duhen T, McGarry Houghton A, Newell E, Gottardo R, Riddell SR. Cancer Cell 40: 2022 393-409.e9	52
Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1<sup>+</sup> T lymphocyte niches through a feed-forward loop. Hua Y, Vella G, Rambow F, Allen E, Antoranz Martinez A, Duhamel M, Takeda A, Jalkanen S, Junius S, Smeets A, Nittner D, Dimmeler S, Hehlgans T, Liston A, Bosisio FM, Floris G, Laoui D, Hollmén M, Lambrechts D, Merchiers P, Marine JC, Schlenner S, Bergers G. Cancer Cell 40: 2022 1600-1618.e10	51
Integrated Analysis of Single-Cell and Bulk RNA-Sequencing Reveals a Tissue-Resident Macrophage-Related Signature for Predicting Immunotherapy Response in Breast Cancer Patients. Xia ZA, Zhou Y, Li J, He J. Cancers (Basel) 14: 2022 5506	3
The tumor microenvironment and triple-negative breast cancer aggressiveness: shedding light on mechanisms and targeting. Furukawa N, Stearns V, Santa-Maria CA, Popel AS. Expert Opin Ther Targets 26: 2022 1041-1056	3
Orthogonal cytokine engineering enables novel synthetic effector states escaping canonical exhaustion in tumor-rejecting CD8<sup>+</sup> T cells. Corria-Osorio J, Carmona SJ, Stefanidis E, Andreatta M, Ortiz-Miranda Y, Muller T, Rota IA, Crespo I, Seijo B, Castro W, Jimenez-Luna C, Scarpellino L, Ronet C, Spill A, Lanitis E, Romero P, Luther SA, Irving M, Coukos G. Nat Immunol 24: 2023 869-883	17
Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance. Chu Y, Dai E, Li Y, Han G, Pei G, Ingram DR, Thakkar K, Qin JJ, Dang M, Le X, Hu C, Deng Q, Sinjab A, Gupta P, Wang R, Hao D, Peng F, Yan X, Liu Y, Song S, Zhang S, Heymach JV, Reuben A, Elamin YY, Pizzi MP, Lu Y, Lazcano R, Hu J, Li M, Curran M, Futreal A, Maitra A, Jazaeri AA, Ajani JA, Swanton C, Cheng XD, Abbas HA, Gillison M, Bhat K, Lazar AJ, Green M, Litchfield K, Kadara H, Yee C, Wang L. Nat Med 29: 2023 1550-1562	66
CD25high Effector Regulatory T Cells Hamper Responses to PD-1 Blockade in Triple-Negative Breast Cancer. Fattori S, Le Roy A, Houacine J, Robert L, Abes R, Gorvel L, Granjeaud S, Rouvière MS, Ben Amara A, Boucherit N, Tarpin C, Pakradouni J, Charafe-Jauffret E, Houvenaeghel G, Lambaudie E, Bertucci F, Rochigneux P, Gonçalves A, Foussat A, Chrétien AS, Olive D. Cancer Res 83: 2023 3026-3044	4
Obesity-associated changes in molecular biology of primary breast cancer. Nguyen HL, Geukens T, Maetens M, Aparicio S, Bassez A, Borg A, Brock J, Broeks A, Caldas C, Cardoso F, De Schepper M, Delorenzi M, Drukker CA, Glas AM, Green AR, Isnaldi E, Eyfjörð J, Khout H, Knappskog S, Krishnamurthy S, Lakhani SR, Langerod A, Martens JWM, McCart Reed AE, Murphy L, Naulaerts S, Nik-Zainal S, Nevelsteen I, Neven P, Piccart M, Poncet C, Punie K, Purdie C, Rakha EA, Richardson A, Rutgers E, Vincent-Salomon A, Simpson PT, Schmidt MK, Sotiriou C, Span PN, Tan KTB, Thompson A, Tommasi S, Van Baelen K, Van de Vijver M, Van Laere S, Van't Veer L, Viale G, Viari A, Vos H, Witteveen AT, Wildiers H, Floris G, Garg AD, Smeets A, Lambrechts D, Biganzoli E, Richard F, Desmedt C. Nat Commun 14: 2023 4418	12
The expression profiles of signature genes from CD103<sup>+</sup>LAG3<sup>+</sup> tumour-infiltrating lymphocyte subsets predict breast cancer survival. Xia ZA, Lu C, Pan C, Li J, Li J, Mao Y, Sun L, He J. BMC Med 21: 2023 268	4
Performance of tumour microenvironment deconvolution methods in breast cancer using single-cell simulated bulk mixtures. Tran KA, Addala V, Johnston RL, Lovell D, Bradley A, Koufariotis LT, Wood S, Wu SZ, Roden D, Al-Eryani G, Swarbrick A, Williams ED, Pearson JV, Kondrashova O, Waddell N. Nat Commun 14: 2023 5758	11
Supervised discovery of interpretable gene programs from single-cell data. Kunes RZ, Walle T, Land M, Nawy T, Pe'er D. Nat Biotechnol 42: 2024 1084-1095	14
Sex disparities revealed by single-cell and bulk sequencing and their impacts on the efficacy of immunotherapy in esophageal cancer. Yan H, Huang J, Li Y, Zhao B. Biol Sex Differ 15: 2024 22	1
A Subpopulation of Luminal Progenitors Secretes Pleiotrophin to Promote Angiogenesis and Metastasis in Inflammatory Breast Cancer. Zhang M, Zhou K, Wang Z, Liu T, Stevens LE, Lynce F, Chen WY, Peng S, Xie Y, Zhai D, Chen Q, Shi Y, Shi H, Yuan Z, Li X, Xu J, Cai Z, Guo J, Shao N, Lin Y. Cancer Res 84: 2024 1781-1798	0
Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects. Menachem A, Alteber Z, Cojocaru G, Fridman Kfir T, Blat D, Leiderman O, Galperin M, Sever L, Cohen N, Cohen K, Granit RZ, Vols S, Frenkel M, Soffer L, Meyer K, Menachem K, Galon Tilleman H, Morein D, Borukhov I, Toporik A, Perpinial Shahor M, Tatirovsky E, Mizrachi A, Levy-Barda A, Sadot E, Strenov Y, Eitan R, Jakobson-Setton A, Yanichkin N, Ferre P, Ophir E. Cancer Immunol Res 12: 2024 687-703	1
C5aR1 inhibition reprograms tumor associated macrophages and reverses PARP inhibitor resistance in breast cancer. Li X, Poire A, Jeong KJ, Zhang D, Ozmen TY, Chen G, Sun C, Mills GB. Nat Commun 15: 2024 4485	1
Identification of Hypoxia-ALCAM<sup>high</sup> Macrophage- Exhausted T Cell Axis in Tumor Microenvironment Remodeling for Immunotherapy Resistance. Xun Z, Zhou H, Shen M, Liu Y, Sun C, Du Y, Jiang Z, Yang L, Zhang Q, Lin C, Hu Q, Ye Y, Han L. Adv Sci (Weinh) 11: 2024 e2309885	1
Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome. Guimarães GR, Maklouf GR, Teixeira CE, de Oliveira Santos L, Tessarollo NG, de Toledo NE, Serain AF, de Lanna CA, Pretti MA, da Cruz JGV, Falchetti M, Dimas MM, Filgueiras IS, Cabral-Marques O, Ramos RN, de Macedo FC, Rodrigues FR, Bastos NC, da Silva JL, Lummertz da Rocha E, Chaves CBP, de Melo AC, Moraes-Vieira PMM, Mori MA, Boroni M. Nat Commun 15: 2024 5694	1
Deciphering breast cancer dynamics: insights from single-cell and spatial profiling in the multi-omics era. Xiong X, Wang X, Liu CC, Shao ZM, Yu KD. Biomark Res 12: 2024 107	0
Multiomics and single-cell sequencings reveal the specific biological characteristics of low Ki-67 triple-negative breast cancer. Han B, Han X, Luo H, Nasir J, Chen C, Shao Z, Ling H, Hu X. Cancer Innov 3: 2024 e146	0