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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Galpin, K. J. C., Rodriguez, G. M., Maranda, V., Cook, D. P., Macdonald, E. A., Murshed, H., Zhao, S., McCloskey, C. W., Chruscinski, A. J., Levy, G. A., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-51217-1 · Cited by 21
PD1hi CD200hi CD4+ exhausted T cell increase immunotherapy resistance and tumour progression by promoting epithelial–mesenchymal transition in bladder cancer
Wu, C. J., Duan, L., Li, H., Liu, X., Cai, T., Yang, Y., Yin, Y., Chang, W., Zhong, L., Zhang, L., et al. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1303 · Cited by 20
“36 In contrast, GZMA and CST7 were specifically expressed in the CD4 Tex1 cluster, suggesting that the subcluster has an immunological effect to a certain extent (Figure 1E; Table S4).”
Background
A spatial map of human macrophage niches reveals context-dependent macrophage functions in colon and breast cancer.Preprint
Matusiak, M., Hickey, J. W., Luca, B. A., Lu, G., Kidziński, Ł., Zhu, S., Colburg, D. R. C., Phillips, D. J., Brubaker, S. W., Charville, G. W., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-2393443/v1 · Cited by 23
Single-cell sequencing reveals the cell map and transcriptional network of sporadic vestibular schwannoma
Chu, Y.-D., Chen, L., Deng, H.-X., Li, Y.-G., & Shen, Z.-S. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.984529 · Cited by 20
Clinical application of single‐cell RNA sequencing in disease and therapy
Nadukkandy, A. S., Kalaiselvan, S., Lin, L., & Luo, Y. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70512 · Cited by 21
“255 One of the major ways to modify the experimental setup to study temporal ordering is to infer the relative age of the mRNA transcript being sequenced.”
Mature and migratory dendritic cells promote immune infiltration and response to anti-PD-1 checkpoint blockade in metastatic melanoma
Yang, J., Wang, C., Fu, D., Ho, L., Galani, K., Chen, L., Gonzalez, J., Fu, J. Y. L., Huang, A. Y., Frederick, D. T., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62878-5 · Cited by 28
Induction of tertiary lymphoid structures in tumor microenvironment to improve anti-tumoral immune checkpoint blockade efficacy
Vion, R., Dugage, M. R., Flippot, R., Ouali, K., Rouanne, M., Clatot, F., Sellars, M., Champiat, S., Chaput, N., Massard, C., et al. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.115572 · Cited by 21
Cell Identity and Spatial Distribution of PD‐1/PD‐L1 Blockade Responders
Li, X., Liu, Y., Gui, J., Gan, L., & Xue, J. (2024) · Advanced Science · doi:10.1002/advs.202400702 · Cited by 17
A Clinically Feasible Diagnostic Typing of Breast Cancer Built on a Homogeneous Electrochemical Biosensor for Simultaneous Multiplex Detection.
Zhang, Y., Ma, W.-H., Li, N., Yang, M., Hou, C.-J., & Huo, D. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.4c01877 · Cited by 19
The impact of Foxp3 + regulatory T‐cells on CD8 + T‐cell dysfunction in tumour microenvironments and responses to immune checkpoint inhibitors
Attias, M., & Piccirillo, C. A. (2024) · British Journal of Pharmacology · doi:10.1111/bph.16313 · Cited by 17
“Furthermore, Tcf-1 expression by CD8 + TILs pretreatment was associated with T-cell expansion posttreatment (Bassez et al., 2021).”
Modulator of TMB-associated immune infiltration (MOTIF) predicts immunotherapy response and guides combination therapy
Qian, Z.-Y., Pan, Y., Li, X., Chen, Y., Wu, H., Liu, Z., Košař, M., Bártek, J., Wang, Z., & Xu, R. (2024) · 中国科学通报：英文版 · doi:10.1016/j.scib.2024.01.025 · Cited by 19
Progress and Challenges of Immunotherapy Predictive Biomarkers for Triple Negative Breast Cancer in the Era of Single-Cell Multi-Omics
Yu, J., Zhikun, G., & Wang, L. (2023) · Life · doi:10.3390/life13051189 · Cited by 22
“Inhibitory macrophages (CX3CR1+, C3+) were inversely correlated with T cell expansion, which shows limited ICIs response [29].”
BackgroundInfluential
Shining a LIGHT on myeloid cell targeted immunotherapy.
Shuptrine, C. W., Perez, V. M., Selitsky, S. R., Schreiber, T. H., & Fromm, G. (2023) · European Journal of Cancer · doi:10.1016/j.ejca.2023.03.040 · Cited by 19
TCR sequencing: applications in immuno-oncology research
Fernández-Sanromán, Á., Joshi, K., Au, L., Chain, B., & Turajlic, S. (2023) · Immuno-Oncology Technology · doi:10.1016/j.iotech.2023.100373 · Cited by 26
“This finding was validated in baseline biopsies from an external cohort of metastatic melanoma patients (n 1⁄4 106) treated with anti-PD-1 or sequential anti-PD-1/anti-cytotoxic T-lymphocyteeassociated antigen 4 (CTLA-4).(58) In breast cancer, Bassez et al.”
Method
Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer
Liu, X., Bai, M., Li, H., Ye, P., Duan, X., Wu, C., Huang, Z., Lu, S., Zhang, J., Zhao, Z., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.965342 · Cited by 19
Single-Cell RNA sequencing reveals immune cell dynamics and local intercellular communication in acute murine cardiac allograft rejection
Chen, Z., Xu, H., Li, Y., Zhang, X., Cui, J., Zou, Y., Yu, J., Wu, J., & Xia, J. (2022) · Theranostics · doi:10.7150/thno.75543 · Cited by 23
“For example, the combination of multiple single-cell omic technologies identified various immunophenotypes and associated gene sets that were positively or negatively correlated with T cell expansion following anti-PD1 treatment in breast cancer [6].”
BackgroundInfluential
Update on lymphocyte-activation gene 3 (LAG-3) in cancers: from biological properties to clinical applications
Zhao, L., Wang, H., Xu, K., Liu, X., & He, Y. (2022) · Chinese Medical Journal · doi:10.1097/cm9.0000000000001981 · Cited by 24
“Elevated LAG-3 in tissues was found to be a biomarker of resistance to ICIs in breast cancers and mouse cancer models.([94,95]) Moreover, high baseline sLAG-3 was associated with poorer PFS in HNSCC patients receiving ICIs or chemotherapy.”
Background
The Comprehensive “Omics” Approach from Metabolomics to Advanced Omics for Development of Immune Checkpoint Inhibitors: Potential Strategies for Next Generation of Cancer Immunotherapy
Yoon, S. J., Lee, C. B., Chae, S. U., Jo, S. J., & Bae, S. K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136932 · Cited by 27
CIDER: an interpretable meta-clustering framework for single-cell RNA-seq data integration and evaluation
Hu, Z., Ahmed, A. A., & Yau, C. (2021) · Genome biology · doi:10.1186/s13059-021-02561-2 · Cited by 17
“Availability of data and materials Raw data are available from SRA under accession number SRP073767 [19]; GEO under accession numbers GSE84133 [21], GSE149689 [22], GSE94820 [24], GSE81682 [25], and GSE72857 [26]; and the European Genome-phenome Archive (EGA) under accession number EGAD00001006608 [23].”
BackgroundMethod
Thyroid cancer: From molecular insights to therapy (Review)
Li, Z., Wang, N., Li, X., Xie, Y., Dou, Z., Xin, H., Lin, Y., Si, Y., Feng, T., & Wang, G. (2025) · Oncology Letters · doi:10.3892/ol.2025.15266 · Cited by 20
Deciphering breast cancer dynamics: insights from single-cell and spatial profiling in the multi-omics era
Xiong, X., Wang, X., Liu, C., Shao, Z.-M., & Yu, K. (2024) · Biomarker Research · doi:10.1186/s40364-024-00654-1 · Cited by 21
“Bassez A et al. [269] treated 29 newly diagnosed patients and 11 patients undergoing neoadjuvant chemotherapy with anti-PD-1 antibodies for about ten days.”
Background
Immunological Mechanisms behind Anti-PD-1/PD-L1 Immune Checkpoint Blockade: Intratumoral Reinvigoration or Systemic Induction?
Zhikun, G., Yu, J., Chen, Z., Chen, S., & Wang, L. (2024) · Biomedicines · doi:10.3390/biomedicines12040764 · Cited by 19
“By contrast, naive or effector/memory T cells, and inhibitory (CX3CR1 + ) macrophages, were inversely correlated [37].”
Background
Deciphering the molecular and clinical characteristics of TREM2, HCST, and TYROBP in cancer immunity: A comprehensive pan-cancer study
Zheng, P., Tan, Y., Liu, Q., Wu, C., Kang, J., Liang, S., Zhu, L., Yan, K., Zeng, L., & Chen, B. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26993 · Cited by 19
“TREM2 has been identified as a specific marker of tumor-associated macrophages (TAM) in the tumor microenvironment, which is consistent across various human cancers and tumor models, including hepatocellular carcinoma, lung cancer, and breast cancer [8 – 10].”
Background
IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia
Huuhtanen, J., Ilander, M. M., Yadav, B., Dufva, O., Lähteenmäki, H., Kasanen, T., Klievink, J., Olsson‐Strömberg, U., Stentoft, J., Richter, J., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci152585 · Cited by 23
“Like in other trajectory analyses (27, 28), we noted 2 different maturation endpoints for CD8+ T cells in the scRNA-seq data stemming from naive CD8+ T cells (cluster 8).”
Result
Dysregulated ligand–receptor interactions from single-cell transcriptomics
Liu, Q., Hsu, C., Li, J., & Shyr, Y. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btac294 · Cited by 20
Significance of intratumoral infiltration of B cells in cancer immunotherapy: From a single cell perspective.
Gu, S., Qian, L., Zhang, Y., Chen, K., Li, Y., Wang, J., & Wang, P. (2021) · Biochimica et biophysica acta. Reviews on cancer · doi:10.1016/j.bbcan.2021.188632 · Cited by 18
The antitumor mechanism of polysaccharides through regulating the microbiota-metabolism-immune axis and their clinical application strategies
Yang, M., Mao, S., Duan, J., & Xiao, P. (2025) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2025.124723 · Cited by 18
Insights into the Mechanisms of Immune‐Checkpoint Inhibitors Gained from Spatiotemporal Dynamics of the Tumor Microenvironment
Zhang, Y., & Liu, Z. (2025) · Advanced Science · doi:10.1002/advs.202508692 · Cited by 13
Serial single-cell RNA sequencing unveils drug resistance and metastatic traits in stage IV breast cancer
Otsuji, K., Takahashi, Y. K., Osako, T., Kobayashi, T., Takano, T., Saeki, S., Yang, L., Baba, S., Kumegawa, K., Suzuki, H., et al. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00723-6 · Cited by 19
Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer
Bullock, K. K., & Richmond, A. J. (2024) · Cancers · doi:10.3390/cancers16122189 · Cited by 18
Network-based screening identifies sitagliptin as an antitumor drug targeting dendritic cells
Ng, I.-I., Zhang, J., Tian, T., Qi, P., Huang, Z., Xiao, K., Yao, X., Ng, L., Zeng, J., & Tang, H. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-008254 · Cited by 17
Multi-scale characterisation of homologous recombination deficiency in breast cancer
Jacobson, D. H., Shi, P., Fisher, J., & Secrier, M. (2023) · Genome Medicine · doi:10.1186/s13073-023-01239-7 · Cited by 18
“Across the Qian et al. cohort and 31 treatment-naïve samples obtained from the Bassez et al. cohort [49], on average 10.7% and 11.2% genes from the signature were expressed per cancer cell, respectively (Additional file 1: Fig.”
BackgroundMethodInfluential
Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation—Immune signature correlates with response
Apostolova, P., Kreutmair, S., Toffalori, C., Punta, M., Unger, S., Burk, A., Wehr, C., Maas‐Bauer, K., Melchinger, W., Haring, E., et al. (2023) · British Journal of Haematology · doi:10.1111/bjh.19007 · Cited by 21
“64 Additionally, we observed reduced expression of CD155 on classical monocytes of responders.”
New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma
Pérez-Lanzón, M., Carbonnier, V., Cordier, P., Palma, F. D. E. D., Petrazzuolo, A., Klein, C., Arbaretaz, F., Mangane, K., Stoll, G., Martins, I., et al. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2023-007117 · Cited by 18
Adenosinergic axis and immune checkpoint combination therapy in tumor: A new perspective for immunotherapy strategy
Fu, R., Liu, X., Liu, X., Shen, H., Xu, X., & Zhao, X. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.978377 · Cited by 15
T cell dysfunction in glioblastoma: a barrier and an opportunity for the development of successful immunotherapies.
Jansen, J. A., Omuro, A. M. P., & Lucca, L. E. (2021) · PubMed · doi:10.1097/wco.0000000000000988 · Cited by 14
“an ongoing antigen-specific response, a pool of central-memory like cells appears to be essential for the efficacy of checkpoint immunotherapy [36], and the jury is still out on whether exhausted TILs can be reinvigorated by anti-PD-1 [37], or are replaced by novel clones [38].”
Background
Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity
Zitti, B., Duval, F., Wirapati, P., Hicham, M., Xie, Y., Oh, J., Hoelzl, J., Meiser, P., Varrone, M., Peterson, H. M., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.11.020 · Cited by 22
Modulation of fibronectin extracellular matrix enhances anti-tumor efficacy of immune checkpoint blockade
Khan, K. A., Caunt, M., Cruz‐Muñoz, W., Li, G., Himmels, P., Xu, P., Kuo, H. Y., Jesudason, R., Gogineni, A., Weimer, R. M., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102322 · Cited by 14
Immunological and pathological characteristics of brain parenchymal and leptomeningeal metastases from non-small cell lung cancer
Zhou, C., Shan, S., Wen, L., Liu, D., Shan, C., Jin, X., Zhou, Z., Li, H., Li, J., Wang, L., et al. (2025) · Cell Discovery · doi:10.1038/s41421-025-00828-7 · Cited by 19
Charge Separation-Engineered Piezoelectric Ultrathin Nanorods Modulate Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Synergistically Piezo-Thermal-Immune Therapy.
Wang, Q., Du, J., Yang, F., Wu, S., Zhu, L.-N., Li, X., Yang, H., Miao, Y.-Q., & Li, Y.-H. (2024) · Small · doi:10.1002/smll.202408038 · Cited by 16
Window of opportunity trials with immune checkpoint inhibitors in triple-negative breast cancer
Quintana, Á., Saini, K. S., Vidal, L., Peg, V., Slebe, F., Loibl, S., Curigliano, G., Schmid, P., & Cortés, J. (2024) · ESMO Open · doi:10.1016/j.esmoop.2024.103713 · Cited by 16
“27 An increase of TILs seems to provide clear evidence that ICIs are reactivating and expanding the immune system of the patient.”
BackgroundMethod
Varied cellular abnormalities in thin vs. normal endometrium in recurrent implantation failure by single-cell transcriptomics
Fu, X., Guo, X., Xu, H., Li, Y., Jin, B., Zhang, X., Shu, C., Fan, Y., Yu, Y., Tian, Y., et al. (2024) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-024-01263-1 · Cited by 14
“NK cells were identified by GNLY and KLRC1 [10], endothelial cells by PECAM1 and VWF [8, 9], T cells by CD3D and GZMK [23, 24], B cells by CD74 and HLA-DRA [25, 26], NK T cells by GZMB and FGFBP2 [27], and pNK cells by PCDH9 and ALDOC [10] (Fig.”
Advances in therapeutic cancer vaccines: Harnessing immune adjuvants for enhanced efficacy and future perspectives
Ren, D., Xiong, S., Ren, Y., Yang, X., Zhao, X., Jin, J., Xu, M., Liang, T., Guo, L., & Weng, L. (2024) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2024.04.054 · Cited by 23
“The strategy is being tested in patients with breast, head, and neck cancers [78].”
Background
ScRNA-seq of gastric cancer tissues reveals differences in the immune microenvironment of primary tumors and metastases
Dong, Y., Hu, K.-S., Zhang, J., Zhu, M.-X., Liu, M.-L., Yuan, Y., Sun, X., Xu, Z.-H., Li, S.-Y., Zhu, Y.-J., et al. (2024) · Oncogene · doi:10.1038/s41388-024-03012-5 · Cited by 16
Bioengineered hydrogels enhance ex vivo preservation of patient-derived tumor explants for drug evaluation
Adine, C., Fernando, K., Ho, N. C. W., Quah, H. S., Ho, S. S. W., Wu, K. Z., Teng, K. W. W., Arcinas, C., Li, L., Ha, K., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2023.122460 · Cited by 19
Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment
Wu, S., Huang, H., Sun, R., Gao, D. S., Ye, F., Huang, J., Li, E., Ni, A., Lu, K. G., Chen, K., et al. (2023) · Cancer Research Communications · doi:10.1158/2767-9764.crc-23-0012 · Cited by 17
Hierarchical transcriptional network governing heterogeneous T cell exhaustion and its implications for immune checkpoint blockade
Tian, W., Qin, G., Jia, M., Li, W., Cai, W., Wang, H., Zhao, Y., Bao, X., Wei, W., Zhang, Y., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1198551 · Cited by 16
“The TCF-1PD-1 Tex cluster exhibits a self-renewing capacity and maintains persistent T cell responses (18, 21, 22, 28, 29) in chronic infections and cancers.”
Background
Upconversion Nanoplatform Enables Multimodal Imaging and Combinatorial Immunotherapy for Synergistic Tumor Treatment and Monitoring.
Gu, M., Zhang, L.-L., Hao, L.-Y., Wang, K., Yang, W., Liu, Z.-Q., Lei, Z.-X., Zhang, Y.-M., Li, W., Jiang, L., et al. (2023) · ACS Applied Materials and Interfaces · doi:10.1021/acsami.2c22420 · Cited by 16
Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer
Brahim, S., Negulescu, A., Geneste, C., Schott, T., Lin, S., Morel, L.-O., Rama, N., Gadot, N., Treilleux, I., Mehlen, P., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05674-7 · Cited by 16
“Next, we therefore used published data of single-cell sequencing [20] to assess the expression of Notch3 in the different compartments of tumors.”
Method
Single-cell screens identify ADAM12 as a fibroblast checkpoint impeding anti-tumor immunity
Li, J., Liu, H., Guo, Q., Zhang, Y., Li, J., Diao, T., Zheng, L., Deng, Z., Yang, Y., Chen, X., et al. (2026) · Cancer Cell · doi:10.1016/j.ccell.2025.12.018 · Cited by 16
Tebentafusp elicits on-target cutaneous immune responses driven by cytotoxic T cells in uveal melanoma patients
Staeger, R., Tastanova, A., Ghosh, A., Winkelbeiner, N., Shukla, P., Kolm, I., Turko, P., Benlahrech, A., Harper, J. V., Broomfield, A., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci181464 · Cited by 16
“The following signatures were used: gylcol-ysis: ENO1 , GAPDH , PGK1 , PKM , and LDHA (98); cytotoxicity: GZMA , GZMB , PRF1, NKG7 (99); IFN-γ signaling: MSigDB hallmark gene set (100); pigmentation: GO:0043473 (101); apoptosis: Kyoto Encyclopedia of Genes and Genomes (KEGG) hsa04210, 87 genes…”
Uncovering gene and cellular signatures of immune checkpoint response via machine learning and single-cell RNA-seq
Pinhasi, A., & Yizhak, K. (2025) · npj Precision Oncology · doi:10.1038/s41698-025-00883-z · Cited by 15
Enriched pathways in gut microbiome predict response to immune checkpoint inhibitor treatment across demographic regions and various cancer types
Cai, X., Cho, J. Y., Chen, L., Liu, Y., Ji, F., Salgado, K., Ge, S., Yang, D., Yu, H., Shao, J., et al. (2025) · iScience · doi:10.1016/j.isci.2025.112162 · Cited by 16
Targeting SNRNP200-induced splicing dysregulation offers an immunotherapy opportunity for glycolytic triple-negative breast cancer
Yang, W.-X., Hong, L., Guo, L.-W., Wang, Y.-J., Han, X.-C., Han, B.-Y., Xing, Z., Zhang, G.-L., Zhou, H., Chen, C., et al. (2024) · Cell Discovery · doi:10.1038/s41421-024-00715-7 · Cited by 15
“The ﬁ rst dataset included 13 TNBC patients treated with pembrolizumab (BioKey study, ClinicalTrials.gov: NCT03197389), whereas the second comprised 7 treatment-naïve TNBC patients (GSE176078) 30,31 .”
Single-cell RNA-sequencing reveals a unique landscape of the tumor microenvironment in obesity-associated breast cancer
Zhao, G., Zhang, X., Meng, L., Dong, K., Shang, S., Jiang, T., Liu, Z., & Gao, H. (2024) · Oncogene · doi:10.1038/s41388-024-03161-7 · Cited by 16
Single-cell sequencing reveals distinct immune cell features in cutaneous lesions of pemphigus vulgaris and bullous pemphigoid
Hu, Z. Q., Zheng, M., Guo, Z., Zhou, W., Zhou, W., Nan, Y., Zhang, G., Lu, Q., & Zhao, M. (2024) · Clinical Immunology · doi:10.1016/j.clim.2024.110219 · Cited by 17
Associations of PD-1 and PD-L1 gene polymorphisms with cancer risk: a meta-analysis based on 50 studies
Yang, M., Liu, Y., Zheng, S.-S., Geng, P., He, T.-L., Lu, L., Feng, Y., & Jiang, Q. (2024) · Aging · doi:10.18632/aging.205689 · Cited by 15
Integrated cancer cell-specific single-cell RNA-seq datasets of immune checkpoint blockade-treated patientsPreprint
Gondal, M. N., Cieslik, M. P., & Chinnaiyan, A. M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.01.17.576110 · Cited by 6
“These studies encompassed various cancer types, including skin cancers such as melanoma 16,17,19 , basal cell carcinoma 20 , melanoma brain metastases 18 , as well as breast cancer, subtypes triple negative 21 , HER2-positive 21 , ER-positive 21 .”
Influential
Photodynamic therapy improves the outcome of immune checkpoint inhibitors via remodelling anti-tumour immunity in patients with gastric cancer
Yu, Y., Xu, B., Xiang, L., Ding, T., Wang, N., Yu, R., Gu, B., Gao, L., Maswikiti, E. P., Wang, Y.-P., et al. (2023) · Gastric Cancer · doi:10.1007/s10120-023-01409-x · Cited by 15
Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy
Lan, X., Liang, J.-G., Wen, C., Quan, X.-L., Lin, H.-W., Xu, Q.-Q., Chen, P.-X., Yao, G., Zhou, D., & Yu, M. (2023) · Chinese Chemical Letters · doi:10.1016/j.cclet.2023.108616 · Cited by 15
Single-cell RNA sequencing reveals a novel inhibitory effect of ApoA4 on NAFL mediated by liver-specific subsets of myeloid cells
Liu, X.-H., Zhou, J., Yan, C., Cheng, C., Fan, J., Xu, J., Zheng, Q., Baï, Q., Li, Z., Li, S., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1038401 · Cited by 17
“Frontiers in Immunology 06 inflammatory macrophages (24), while complement C3 expressed by Cx3cr1 macrophages suppresses the infiltration and function of CD8 T cells and CD4 T cells (25).”
Background
Improvement of TNBC immune checkpoint blockade with a microwave-controlled ozone release nanosystem.
Song, L., Zheng, D., Xu, J.-S., Xu, T., Liu, Z., Zhang, H., Li, Y., Peng, Y., & Shi, H.-B. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.09.053 · Cited by 15
Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood
Wall, I., Boulat, V., Shah, A., Blenman, K., Wu, Y., Alberts, E., Calado, D. P., Salgado, R., & Grigoriadis, A. E. (2022) · Cancers · doi:10.3390/cancers14184505 · Cited by 16
“Two recent studies provide single-cell atlases of the immune landscape of breast cancer patients before and after treatment with chemo-immunotherapy regimens [146].”
Background
Immune checkpoint blockade provokes resident memory T cells to eliminate head and neck cancer.
Veatch, J. R., & Riddell, S. (2022) · Cell · doi:10.1016/j.cell.2022.07.006 · Cited by 15
Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines
Hensler, M., Raková, J., Kašíková, L., Lanickova, T., Pasulka, J., Holicek, P., Hraška, M., Hrnciarova, T., Kadlecová, P., Schoenenberger, A., et al. (2022) · Oncoimmunology · doi:10.1080/2162402x.2022.2101596 · Cited by 15
Self-citation
Targeting the tumor microenvironment in triple-negative breast cancer: Biological insights and therapeutic opportunities
Martorana, T. M., Ricciardi, G., Tralongo, P., Fiorentino, V., Pizzimenti, C., Franchina, M., Marino, M. A., Santarpía, M., Tuccari, G., Ieni, A., et al. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.156226 · Cited by 15
Spatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer
Oh, J., Hoelzl, J., Carlson, J. C. T., Bill, R., Peterson, H. M., Faquin, W., Pittet, M., Pai, S. I., & Weissleder, R. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102100 · Cited by 14
“22 In addition, the enrichment of CCR7 + DCs in pretreatment biopsy samples from patients with breast cancer was implicated in the expansion of tumor-infiltrating T cells after treatment 62 and in patients with hepatocellular carcinoma who responded to neoadjuvant anti-PD-1 therapy.”
PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway
Hodgins, J. J., Abou‐Hamad, J., O’Dwyer, C., Hagerman, A., Yakubovich, E., de Souza, C. T., Marotel, M., Buchler, A., Fadel, S., Park, M. M., et al. (2024) · The Journal of Experimental Medicine · doi:10.1084/jem.20221721 · Cited by 19

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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