Cited by 867Cancer Immunotherapy and BiomarkersBreast Cancer Treatment StudiesT-cell and B-cell Immunology

A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer

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Bassez, Ayse, Vos, Hanne, Van Dyck, Laurien, Floris, Giuseppe, Arijs, Ingrid, Desmedt, Christine, Boeckx, Bram, Vanden Bempt, Marlies +9 more·2021·Nature Medicine

Abstract

Immune-checkpoint blockade (ICB) combined with neoadjuvant chemotherapy improves pathological complete response in breast cancer. To understand why only a subset of tumors respond to ICB, patients with hormone receptor-positive or triple-negative breast cancer were treated with anti-PD1 before surgery. Paired pre- versus on-treatment biopsies from treatment-naive patients receiving anti-PD1 (n = 29) or patients receiving neoadjuvant chemotherapy before anti-PD1 (n = 11) were subjected to single-cell transcriptome, T cell receptor and proteome profiling. One-third of tumors contained PD1-expressing T cells, which clonally expanded upon anti-PD1 treatment, irrespective of tumor subtype. Expansion mainly involved CD8+ T cells with pronounced expression of cytotoxic-activity (PRF1, GZMB), immune-cell homing (CXCL13) and exhaustion markers (HAVCR2, LAG3), and CD4+ T cells characterized by expression of T-helper-1 (IFNG) and follicular-helper (BCL6, CXCR5) markers. In pre-treatment biopsies, the relative frequency of immunoregulatory dendritic cells (PD-L1+), specific macrophage phenotypes (CCR2+ or MMP9+) and cancer cells exhibiting major histocompatibility complex class I/II expression correlated positively with T cell expansion. Conversely, undifferentiated pre-effector/memory T cells (TCF7+, GZMK+) or inhibitory macrophages (CX3CR1+, C3+) were inversely correlated with T cell expansion. Collectively, our data identify various immunophenotypes and associated gene sets that are positively or negatively correlated with T cell expansion following anti-PD1 treatment. We shed light on the heterogeneity in treatment response to anti-PD1 in breast cancer.

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Crossref · 10.1038/s41591-021-01323-8

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  • These CD8+ T cell subsets show different responses to anti-PD(L)-1 therapies, with TCF7+ Tpex cells demonstrated critical for ICB response in mouse tumor models and cancers.

    “These cell subsets show different responses to anti-PD(L)-1 therapies,”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [17]

    The section ‘T-cells expressing PD1 proliferate after anti-PD1 treatment’ reports that CD8+ T-cell phenotypes differed in expansion following treatment, supporting the citing sentence’s general point. But the paper does not demonstrate that TCF7+ Tpex cells are critical for ICB response in mouse tumor models or cancers; its ‘Immune environment associated with T-cell expansion’ section instead reports an inverse correlation between pretreatment TCF7 expression and T-cell expansion in the breast-cancer patients studied. Page numbers are unavailable in our copy. (LLM, conf=0.87)

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  • Applying ICB and combination therapies as neoadjuvant treatments provides an opportunity to observe immune cell dynamics in the tumor microenvironment with temporal samples.

    “Applying ICB and combination therapies as neoadjuvant treatments provides an opportunity to observe immune cell dynamics in tumor microenvironment (TME) with temporal samples.”

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Research works printed but not linked: 7

  1. Street, K., et al. Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics 19, 477 (2018).
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Authors
Bassez, A., Vos, H., Van Dyck, L., Floris, G., Arijs, I., Desmedt, C., Boeckx, B., Vanden Bempt, M., Nevelsteen, I., Lambein, K., Punie, K., Neven, P., Garg, A. D., Wildiers, H., Qian, J., Smeets, A., & Lambrechts, D.
Affiliations
  • VIB-KU Leuven Center for Cancer Biology (BE)
  • KU Leuven (BE)
  • Universitair Ziekenhuis Leuven (BE)
  • Women's Hospital, School of Medicine, Zhejiang University (CN)
Corresponding author
  • Qian, Junbin
  • Smeets, Ann
  • Lambrechts, Diether
Venue
Nature Medicine
Published
2021-05
Volume
27
Issue
5
Pages
820-832
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W3157384750
Cited by
867
References
74
Citations by year
2026: 156 · 2025: 168 · 2024: 234 · 2023: 159 · 2022: 116 · 2021: 33
FWCI
52.64
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
Funders
  • Vlaams Supercomputer Centrum
  • European Commission (847912)
  • Fonds Wetenschappelijk Onderzoek (KOTK/2018/11509/1, C14/18/092, POR/16/040, G0B4620N, C14/19/098, 30837538, G0B6120N)
  • KU Leuven (C14/19/098, C14/18/092, POR/16/040, C14/19, 30837538, KOTK/2018/11509/1)
  • Kom op tegen Kanker (C14/19/098, 30837538, POR/16/040, KOTK/2018/11509/1)
  • Vlaamse regering (VR 2016 2312 Doc.1521/4, 30837538, C14/19/098)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
breast cancer, anti-PD-1 therapy, immune checkpoint blockade, neoadjuvant chemotherapy, tumor immune microenvironment, T cell clonal expansion, CD8+ T cells, CD4+ T cells, T cell exhaustion, tumor-infiltrating macrophages, treatment response heterogeneity, triple-negative breast cancer, hormone receptor-positive breast cancer, single-cell transcriptomics, proteomics
MeSH terms
Immune Checkpoint Inhibitors, Dendritic Cells, Female, Humans, Macrophages, Receptors, Antigen, T-Cell, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Neoadjuvant Therapy, Single-Cell Analysis, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized, Triple Negative Breast Neoplasms

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