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

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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, Nevelsteen, Ines, Lambein, Kathleen, Punie, Kevin, Neven, Patrick, Garg, Abhishek D., Wildiers, Hans, Qian, Junbin, Smeets, Ann, Lambrechts, Diether·2021·Nature Medicine

DOI 10.1038/s41591-021-01323-8

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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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A single-cell atlas reveals immune heterogeneity in anti-PD-1-treated non-small cell lung cancer
Liu, Z., Yang, Z., Wu, J., Zhang, W., Sun, Y., Zhang, C., Bai, G., Li, Y., Fan, H., Chen, Y., et al. (2025) · Cell · doi:10.1016/j.cell.2025.03.018 · Cited by 184
“17,50 Thus, it could be difﬁcult to fully understand long-term therapeutic outcomes with pre-treatment TIME information alone.”
Immunotherapy-activated T cells recruit and skewlate-stage activated M1-like macrophagesthat are critical for therapeutic efficacy.
van Elsas, M. J., Middelburg, J., Labrie, C., Roelands, J., Schaap, G., Sluijter, M., Tonea, R., Ovcinnikovs, V., Lloyd, K., Schuurman, J., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.04.011 · Cited by 165
Spatially Segregated Macrophage Populations Predict Distinct Outcomes in Colon Cancer
Matusiak, M., Hickey, J. W., van IJzendoorn, D. G. P., Lu, G., Kidziński, Ł., Zhu, S., Colburg, D. R. C., Luca, B. A., Phillips, D. J., Brubaker, S. W., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-1300 · Cited by 190
“To address this question, we used the scRNA monocyte and macrophage transcriptomes from Bassez and colleagues (23) (Fig.”
Influential
Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma
Liu, Z., Zhang, Y., Ma, N., Yang, Y., Ma, Y., Wang, F., Wang, Y., Wei, J., Chen, H., Tartarone, A., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.09.011 · Cited by 197
Dendritic cell maturation in cancer
Moon, C. Y., Belabed, M., Park, M. D., Mattiuz, R., Puleston, D. J., & Mérad, M. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-024-00787-3 · Cited by 189
Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer
Croizer, H., Mhaidly, R., Kieffer, Y., Gentric, G., Djerroudi, L., Leclère, R., Pelon, F., Robley, C., Bohec, M., Meng, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47068-z · Cited by 183
“These results are added now in the New Fig.”
Influential
B-cell-specific checkpoint molecules that regulate anti-tumour immunity
Bod, L., Kye, Y.-C., Shi, J., Triglia, E. T., Schnell, A., Fessler, J., Ostrowski, S. M., von Franque, M., Kuchroo, J. R., Barilla, R., et al. (2023) · Nature · doi:10.1038/s41586-023-06231-0 · Cited by 188
Antigen-presenting cancer associated fibroblasts enhance antitumor immunity and predict immunotherapy response
Song, J.-Q., Wei, R.-Y., Liu, C.-C., Zhao, Z.-X., Liu, X.-J., Wang, Y.-N., Liu, F.-L., & Liu, X.-W. (2025) · Nature Communications · doi:10.1038/s41467-025-57465-7 · Cited by 151
Cancer immunotherapies transition endothelial cells into HEVs that generate TCF1+ T lymphocyte niches through a feed-forward loop
Hua, Y., Vella, G., Rambow, F., Allen, E., Antoranz, A., Duhamel, M., Takeda, A., Jalkanen, S., Junius, S., Smeets, A., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.11.002 · Cited by 176
Self-citation
Spatial landscapes of cancers: insights and opportunities
Chen, J., Larsson, L., Swarbrick, A., & Lundeberg, J. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-024-00926-7 · Cited by 156
“…across multiple cancer types, comparative serial transcriptional profiling has shed important light on T cell activation and expansion in response to treatment with these agents 99,100 as well as on specific subsets of immune and/or stromal cells associated with response or resistance 100–102 .”
Neoantigen-specific CD4+ T cells in human melanoma have diverse differentiation states and correlate with CD8+ T cell, macrophage, and B cell function
Veatch, J. R., Lee, S. M., Shasha, C., Singhi, N., Szeto, J. L., Moshiri, A. S., Kim, T. S., Smythe, K. S., Kong, P., Fitzgibbon, M., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.03.006 · Cited by 159
Spatial and Temporal Mapping of Breast Cancer Lung Metastases Identify TREM2 Macrophages as Regulators of the Metastatic Boundary
Yofe, I., Shami, T., Cohen, N., Landsberger, T., Sheban, F., Stoler-Barak, L., Yalin, A., Phan, T. S., Li, B., Monteran, L., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0299 · Cited by 130
“In recent years, multiple studies have thoroughly characterized the immune and stromal microenvironment in breast cancer (27, 64–66), but these studies have focused on the primary tumor site.”
Transcriptomic profiles of neoantigen-reactive T cells in human gastrointestinal cancers
Zheng, C., Fass, J. N., Shih, Y.-P., Gunderson, A. J., Silva, N. S., Huang, H., Bernard, B. M., Rajamanickam, V., Slagel, J., Bifulco, C. B., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.03.005 · Cited by 151
MultiNicheNet: a flexible framework for differential cell-cell communication analysis from multi-sample multi-condition single-cell transcriptomics dataPreprint
Browaeys, R., Gilis, J., Sang-aram, C., Bleser, P. D., Hoste, L., Tavernier, S. J., Lambrechts, D., Seurinck, R., & Saeys, Y. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.13.544751 · Cited by 136
“Figure 3 MultiNicheNet prioritizes differences in therapy-induced intercellular communication changes between and within response groups. a) MultiNicheNet was applied to scRNA-seq from Bassez et al. to compare on-therapy versus pre-therapy differences in cell-cell communication between breast cancer patients with T ce…”
MethodInfluentialSelf-citation
High-throughput single-сell sequencing in cancer research
Jia, Q., Chu, H., Jin, Z., Long, H., & Zhu, B. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00990-4 · Cited by 157
“used scTCR-Seq technology to confirm the presence of clonotype expansion in patients after PD-1 inhibitor treatment, indicating a continuous antitumor immune response; tumor cells from patients with clonotype expansion are enriched in pathways such as cell death, proteolysis, and immune signal transduction.(104)”
Method
High endothelial venules in cancer: Regulation, function, and therapeutic implication
Vella, G., Hua, Y., & Bergers, G. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.002 · Cited by 132
Chronic type I interferon signaling promotes lipid-peroxidation-driven terminal CD8+ T cell exhaustion and curtails anti-PD-1 efficacy
Chen, W., Teo, J. M. N., Yau, S. W., Wong, M. Y., Lok, C., Che, C., Javed, A., Huang, Y., Ma, S., & Ling, G. S. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111647 · Cited by 142
CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy
Franken, A., Bila, M., Mechels, A., Kint, S., Dessel, J. V., Pomella, V., Vanuytven, S., Philips, G., Bricard, O., Xiong, J., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.02.007 · Cited by 128
Self-citation
PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes
Nagasaki, J., Inozume, T., Sax, N., Ariyasu, R., Ishikawa, M., Yamashita, K., Kawazu, M., Ueno, T., Irie, T., Tanji, E., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110331 · Cited by 126
Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy
Xia, X., Yang, Z., Lu, Q., Liu, Z., Wang, L., Du, J., Li, Y., Yang, D., & Wu, S. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02079-8 · Cited by 112
PD-L1-expressing tumor-associated macrophages are immunostimulatory and associate with good clinical outcome in human breast cancer
Wang, L., Guo, W., Zhikun, G., Yu, J., Tan, J., Simons, D. L., Hu, K., Liu, X., Zhou, Q., Zheng, Y.-Z., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101420 · Cited by 114
Presence of onco-fetal neighborhoods in hepatocellular carcinoma is associated with relapse and response to immunotherapy
Li, Z., Pai, R., Gupta, S., Currenti, J., Guo, W., Bartolomeo, A. D., Feng, H., Zhang, Z., Li, Z., Liu, L., et al. (2024) · Nature Cancer · doi:10.1038/s43018-023-00672-2 · Cited by 107
“The presence of onco-fetal reprogramming could provide promising opportunities for stratification in early stage HCCs to anticipate relapse and has implications for therapeutically targeting the TME with combined immunotherapy.”
Influential
TCR-independent CD137 (4-1BB) signaling promotes CD8+-exhausted T cell proliferation and terminal differentiation
Pichler, A., Carrié, N., Cuisinier, M., Ghazali, S., Voisin, A., Axisa, P., Tosolini, M., Mazzotti, C., Golec, D. P., Mahéo, S., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.06.007 · Cited by 124
“Analysis of public datasets of CD8 + TIL scRNA-seq from human melanoma 47 and breast cancer 48 confirmed the higher expression of TNFRSF9 on Tex cell clusters (Figures S1K and S1N).”
Background
Single-cell multi-omics in cancer immunotherapy: from tumor heterogeneity to personalized precision treatment
Le, J., Dian, Y., Zhao, D., Guo, Z., Luo, Z., Chen, X., Zeng, F., & Deng, G. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02426-3 · Cited by 118
“…genomics, transcriptomics, epigenomics, proteomics, and spatial transcriptomics [2–5]—researchers can now construct high-resolution cellular atlases of tumors [6, 7] delineate tumor evolutionary trajectories [8, 9] and unravel the intricate regulatory networks within the TME [10, 11].”
Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer
Guo, X., Nie, H., Zhang, W., Li, J., Ge, J., Xie, B., Hu, W., Zhu, Y., Zhong, N., Zhang, X., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.01.001 · Cited by 100
A comprehensive single-cell breast tumor atlas defines epithelial and immune heterogeneity and interactions predicting anti-PD-1 therapy response
Xu, L., Saunders, K., Huang, S.-P., Knútsdóttir, H., Martinez-Algarin, K., Terrazas, I., Chen, K., McArthur, H., Maués, J., Hodgdon, C., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101511 · Cited by 84
Supervised discovery of interpretable gene programs from single-cell data
Kunes, R., Walle, T., Land, M., Nawy, T., & Pe’er, D. (2023) · Nature Biotechnology · doi:10.1038/s41587-023-01940-3 · Cited by 106
PD-1- CD45RA+ effector-memory CD8 T cells and CXCL10+ macrophages are associated with response to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma
Cappuyns, S., Philips, G., Vandecaveye, V., Boeckx, B., Schepers, R., Brussel, T. V., Arijs, I., Mechels, A., Bassez, A., Lodi, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43381-1 · Cited by 97
Self-citation
Mature dendritic cells enriched in immunoregulatory molecules (mregDCs): A novel population in the tumour microenvironment and immunotherapy target
Li, J., Zhou, J., Huang, H., Jiang, J., Zhang, T., & Ni, C. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1199 · Cited by 96
Impaired function of dendritic cells within the tumor microenvironment
Xiao, Z., Wang, R., Wang, X., Yang, H., Dong, J.-M., He, X., Yang, Y., Guo, J., Cui, J., & Zhou, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1213629 · Cited by 105
“MregDCs have also been described in various human cancers, including hepatocellular carcinoma (23), breast cancer (24), colon cancer (25), and gastric cancer (26).”
Background
Topological analysis of hepatocellular carcinoma tumour microenvironment based on imaging mass cytometry reveals cellular neighbourhood regulated reversely by macrophages with different ontogeny
Sheng, J., Zhang, J., Wang, L., Tano, V., Tang, J., Wang, X., Wu, J., Song, J., Zhao, Y., Rong, J., et al. (2021) · Gut · doi:10.1136/gutjnl-2021-324339 · Cited by 107
Exploiting temporal aspects of cancer immunotherapy
Zemek, R. M., Anagnostou, V., da Silva, I. P., Long, G. V., & Lesterhuis, W. J. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00699-2 · Cited by 96
“On the basis of the accumulating data on beneficial immunological effects early after start of chemotherapy, the TONIC study has explored a short induction approach in patients with TNBC involving 2 weeks of radiotherapy, cyclophosphamide, cisplatin, doxorubicin or no induction, followed by anti-PD1 treatment 52 .”
Influential
Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition
Xu, L., Guo, J., Moledina, D., & Cantley, L. (2022) · Nature Communications · doi:10.1038/s41467-022-32634-0 · Cited by 90
Deletion of PD-1 destabilizes the lineage identity and metabolic fitness of tumor-infiltrating regulatory T cells
Kim, M. J., Kim, K., Park, H. J., Kim, G.-R., Hong, K. H., Oh, J. H., Son, J., Park, D. J., Kim, D., Choi, J.-M., et al. (2023) · Nature Immunology · doi:10.1038/s41590-022-01373-1 · Cited by 90
Systematic dissection of tumor-normal single-cell ecosystems across a thousand tumors of 30 cancer types
Kang, J., Lee, J. H., Cha, H., An, J., Kwon, J., Lee, S., Kim, S., Baykan, M. Y., Kim, S. Y., An, D., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48310-4 · Cited by 90
“S3, 4).”
Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis
Neo, S., Tong, L., Chong, J., Liu, Y., Xu, J., Oliveira, M. M. S., Chen, Y., Chen, Z., Lee, K., Burduli, N., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adi2952 · Cited by 91
“Following up on our previous study, the present work reports a subset of CD69 + and perforin low/neg NK sub-set that correlated with myeloid cell abundance in patients who are considered nonresponders to anti–PD-1 therapy from a published dataset ( 30 ).”
Method
Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial
Nederlof, I., Isaeva, O. I., de Graaf, M., Gielen, R., Bakker, N. A. M., Rolfes, A. L., Garner, H., Boeckx, B., Traets, J. J. H., Mandjes, I. A. M., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03249-3 · Cited by 88
Self-citation
Tumor microenvironment and immunotherapy for triple-negative breast cancer
Guo, Z., Zhu, Z., Lin, X., Wang, S., Wen, Y., Wang, L., Zhi, L., & Zhou, J. (2024) · Biomarker Research · doi:10.1186/s40364-024-00714-6 · Cited by 95
Distinct CD8+ T cell dynamics associate with response to neoadjuvant cancer immunotherapies
Li, H., Zandberg, D. P., Kulkarni, A., Chiosea, S. I., Santos, P. M., Isett, B. R., Joy, M., Sica, G., Contrera, K. J., Tatsuoka, C. M., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.02.026 · Cited by 85
Single-cell sequencing reveals trajectory of tumor-infiltrating lymphocyte states in pancreatic cancer
Schalck, A., Sakellariou-Thompson, D., Forget, M.-A., Sei, E., Hughes, T. G., Reuben, A., Bai, S., Hu, M., Kumar, T., Hurd, M. W., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1248 · Cited by 85
A Comprehensive Review of Bioinformatics Tools for Genomic Biomarker Discovery Driving Precision Oncology
Clark, A. J., & Lillard, J. W. (2024) · Genes · doi:10.3390/genes15081036 · Cited by 109
“These technologies allow for high-resolution analysis of gene expression at the individual cell level, investigating the diversity of cell types and interactions within the microenvironment [89].”
Background
Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1
Yang, Z., Liu, X., Zhu, J., Chai, Y., Cong, B., Li, B., Gao, W.-F., Hu, Y., Wen, M., Liu, Y., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.11.008 · Cited by 83
Chemotherapy‐Enabled Colorectal Cancer Immunotherapy of Self‐Delivery Nano‐PROTACs by Inhibiting Tumor Glycolysis and Avoiding Adaptive Immune Resistance
Zhao, L., Zheng, R., Rao, X., Huang, C., Zhou, H., Yu, X., Jiang, X., & Li, S. (2024) · Advanced Science · doi:10.1002/advs.202309204 · Cited by 70
Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8+ T cell exhaustion and anti-PD-1 resistance
Chen, C., Zhao, F., Peng, J., Zhao, D., Xu, L., Li, H., Ma, S., Peng, X., Sheng, X., Sun, Y., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101686 · Cited by 66
Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer
Zheng, S., Zou, Y., Tang, Y., Yang, A., Liang, J.-Y., Wu, L., Tian, W., Xiao, W., Xie, X., Yang, L., et al. (2022) · OncoImmunology · doi:10.1080/2162402x.2021.2020984 · Cited by 92
Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity
Lee, C. Y. C., Kennedy, B. C., Richoz, N., Dean, I., Tuong, Z. K., Gaspal, F., Li, Z., Willis, C., Hasegawa, T., Whiteside, S. K., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-44787-1 · Cited by 82
“1d, 11h) 24 , CCR7_DCs from tumours that successfully underwent clonal T cell expansion following treatment with anti-PD-1 antibodies were enriched in transcripts associated with our ICB-induced Ccr7_DC.2 cluster, versus non-responders (Fig.”
Background
Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome
Guimarães, G. R., Maklouf, G. R., Teixeira, C. E., Santos, L. D. O., Tessarollo, N. G., de Toledo, N. E., Serain, A. F., de Lanna, C. A., Pretti, M. A. M., da Cruz, J. G. V., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49916-4 · Cited by 93
Cuproptosis-immunotherapy using PD-1 overexpressing T cell membrane-coated nanosheets efficiently treats tumor
Liu, T., Zhou, Z., Zhang, M., Lang, P., Li, J., Liu, Z., Zhang, Z., Li, L., & Zhang, L. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.08.055 · Cited by 80
IFNγ-induced stem-like state of cancer cells as a driver of metastatic progression following immunotherapy
Beziaud, L., Young, C. M., Alonso, A. M., Norkin, M., Minafra, A. R., & Huelsken, J. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.05.007 · Cited by 83
Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer
Hsieh, C.-H., Jian, C.-Z., Lin, L., Low, G.-S., Ou, P.-Y., Hsu, C., & Ou, D. (2022) · Cancers · doi:10.3390/cancers14020294 · Cited by 70
“identified several genes that were able to predict a better immune response to anti-PD-1 treatment associated with CXCL13 [126].”
Background
Mapping cellular interactions from spatially resolved transcriptomics data
Zhu, J. J., Wang, Y., Chang, W. Y., Malewska, A., Napolitano, F., Gahan, J. C., Unni, N. G., Zhao, M., Yuan, R., Wu, F., et al. (2024) · Nature Methods · doi:10.1038/s41592-024-02408-1 · Cited by 75
“As we will show later in this work, this is also to be expected as they all participate in inducing the epithelial–mesenchymal transition (EMT) in”
Single-cell RNA sequencing-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma
Cappuyns, S., Piqué‐Gili, M., Esteban-Fabró, R., Philips, G., Balaseviciute, U., Pinyol, R., Gris‐Oliver, A., Vandecaveye, V., Abril‐Fornaguera, J., Montironi, C., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.12.016 · Cited by 81
“Finally, patients were categorized accordingly into molecular subsets predictive of clinical bene ﬁ t or resistance to atezo+bev.”
Self-citation
Discovery of a novel dual-targeting D-peptide to block CD24/Siglec-10 and PD-1/PD-L1 interaction and synergize with radiotherapy for cancer immunotherapy
Shen, W., Shi, P., Dong, Q., Zhou, X., Chen, C., Sui, X., Tian, W., Zhu, X., Wang, X., Jin, S., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-007068 · Cited by 75
Single cell dynamics of tumor specificity vs bystander activity in CD8+ T cells define the diverse immune landscapes in colorectal cancer
Borràs, D. M., Verbandt, S., Ausserhofer, M., Sturm, G., Lim, J., Verge, G. A., Vanmeerbeek, I., Laureano, R. S., Govaerts, J., Sprooten, J., et al. (2023) · Cell Discovery · doi:10.1038/s41421-023-00605-4 · Cited by 67
“Indeed these genes together enriched for various pathways relevant for tumor-reactive exhaustion or multi-factorial tumoral in ﬂ ammation 7,31,42,43 including nuclear factor of activated T cells (NFAT) signaling, IFNG signaling, various IL-based pathways including IL2/IL15, TGF β signaling, and…”
Self-citation
Characteristics of premanufacture CD8+ T cells determine CAR-T efficacy in patients with diffuse large B-cell lymphoma
Wang, Y., Tong, C., Lu, Y., Wu, Z., Guo, Y., Liu, Y., Wei, J., Wang, C., Yang, Q., & Han, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01659-2 · Cited by 81
Robust and Sustained STING Pathway Activation via Hydrogel-Based In Situ Vaccination for Cancer Immunotherapy
Cheng, S.-L., Lee, H.-M., Li, C.-P., Lin, M.-W., Chou, M.-Y., Yen, Y.-T., Wu, T.-H., Lian, Y.-C., Shih, Y., Chiang, C.-S., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c12337 · Cited by 65
Semi-supervised integration of single-cell transcriptomics data
Andreatta, M., Hérault, L., Gueguen, P., Gfeller, D., Berenstein, A. J., & Carmona, S. J. (2024) · Nature Communications · doi:10.1038/s41467-024-45240-z · Cited by 75
“These samples amounted to 11,021 cells covering 7 different tumor types from multiple studies 24 – 32 .”
Single-cell profiling of immune cells after neoadjuvant pembrolizumab and chemotherapy in IIIA non-small cell lung cancer (NSCLC)
Ren, X., Hui, Z., Zhang, J., Ren, Y., LI, X., Yan, C., Wang, T., Yu, W., Wang, T., Xiao, S., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05057-4 · Cited by 74
“Consistent with our findings, Bassez and colleagues [44] performed single-cell sequencing and proteomic analysis of tumor tissue from breast cancer patients before and after anti-PD-1 therapy and demonstrated that CD4 T cells characterized by expression of T helper 1 (IFNG) and Tfh (BCL6, CXCR5) markers clonally expan…”
Result
Emerging mechanisms of the unfolded protein response in therapeutic resistance: from chemotherapy to Immunotherapy
He, J., Zhou, Y. L., & Sun, L. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01438-0 · Cited by 77
“…[16], T-cell immunoreceptor with Ig and ITIM domains (TIGIT) [17], CD160 [18], TNF receptor superfamily member 9 (TNFRSF9) [19], and hepatitis A virus cellular receptor 2 (HAVCR2) [20]; and (2) decreased proliferation, viability, and the loss of cytotoxic activity against tumours in vitro [21].”
Background
Obesity-associated changes in molecular biology of primary breast cancer
Nguyen, H.-L., Geukens, T., Maetens, M., Aparicio, S. A. J. R., Bassez, A., Borg, Å., Brock, J. E., Broeks, A., Caldas, C., Cardoso, F., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39996-z · Cited by 71
Self-citation
Predictive Biomarkers for Response to Immunotherapy in Triple Negative Breast Cancer: Promises and Challenges
Wang, X., Collet, L., Rediti, M., Debien, V., Caluwé, A. D., Venet, D., Romano, E., Rothé, F., Sotiriou, C. P., & Buisseret, L. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12030953 · Cited by 69
Targeting CXCL16 and STAT1 augments immune checkpoint blockade therapy in triple-negative breast cancer
Palakurthi, B., Fross, S. R., Guldner, I. H., Aleksandrovic, E., Liu, X., Martino, A. K., Wang, Q., Neff, R. A., Golomb, S. M., Lewis, C. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37727-y · Cited by 70
“To strengthen the clinical relevance of our ﬁ ndings by which the emergence of trajectory Path 1 myeloid cells (cluster 0 cells) after chemo treatment contribute to breast cancer immune microenvironment in human breast cancer context, we performed in silico analysis using Bassez et al. dataset 23 .”

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
ORCID: Bassez, Ayse
Vos, Hanne
Floris, Giuseppe
Arijs, Ingrid
Desmedt, Christine
Boeckx, Bram
Vanden Bempt, Marlies
Nevelsteen, Ines
Punie, Kevin
Neven, Patrick
Garg, Abhishek D.
Wildiers, Hans
Qian, Junbin
Smeets, Ann
Lambrechts, Diether
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 2021-05
Volume: 27
Issue: 5
Pages: 820-832
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/s41591-021-01323-8
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: green
lirias.kuleuven.be
Licence: other-oa
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer

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