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A single-cell map of intratumoral changes during anti-PD1 treatment of patients with breast cancer
Open accessAbstract
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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“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]
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“Applying ICB and combination therapies as neoadjuvant treatments provides an opportunity to observe immune cell dynamics in tumor microenvironment (TME) with temporal samples.”
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]
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Cited by
Sorted by citations
Items 301–400 of 707
Grasset, E. M., Barillé‐Nion, S., & Juin, P. P. (2024) · Disease Models & Mechanisms · doi:10.1242/dmm.050542 · Cited by 14
“…of immunoregulatory dendritic cells expressing PD-L1, macrophages with specific phenotypes (CCR2 + or MMP9 + ) and cancer cells expressing major histocompatibility complex class I/II before treatment correlated positively with T cell expansion upon immune checkpoint blockade (Bassez et al., 2021).”
Zhou, J., Wan, F., Wang, L., Peng, C. Y., Huang, R., & Peng, F. (2023) · MedComm · doi:10.1002/mco2.464 · Cited by 18
Prognostic significance and mechanisms of CXCL genes in clear cell renal cell carcinoma
Shen, J., Wang, R., Chen, Y., Fang, Z., Tang, J., Yao, J., Gao, J., Chen, X., & shi, X. (2023) · Aging · doi:10.18632/aging.204922 · Cited by 13
Hui, Z., Ren, Y., Zhang, D., Chen, Y., Yu, W., Cao, J., Liu, L., Wang, T., Xiao, S., Zheng, L., et al. (2023) · npj Precision Oncology · doi:10.1038/s41698-023-00384-x · Cited by 21
Kilmartin, D., O’Loughlin, M., Andreu, X., Bagó-Horváth, Z., Bianchi, S., Chmielik, E., Cserni, G., Figueiredo, P., Floris, G., Foschini, M. P., et al. (2021) · Cancers · doi:10.3390/cancers13174410 · Cited by 14
“The number of lymphocytes seems to increase after only one dose of immune therapy and is associated with significant clonotype changes in T cells suggesting activation of T cells based on the expression of immune-check point, effector, and cytotoxic markers [38].”
BackgroundSelf-citationMa, Q., Wang, J., & Jiang, Q. (2026) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-06056-2 · Cited by 13
“Bassez [ 43] and Lambrechtslab cohort [ 44 ] of scRNA data were collected from lambrechtslab website.”
From Lymphotoxin to Tertiary Lymphoid Structures and Beyond
Ruddle, N. (2025) · Immunological Reviews · doi:10.1111/imr.70062 · Cited by 13
“TLSs were not directly evaluated in this study, it is likely that results are indicative of their presence [118].”
Guo, K., Yang, L., Huang, Z., Qian, K., Shi, Y., Fei, M., Feng, Y., Chen, Z., Qiu, M., Tang, L., et al. (2025) · Advanced Science · doi:10.1002/advs.202417672 · Cited by 10
Trajectories of macrophage ontogeny and reprogramming in cancer
Duval, F., Lourenço, J., Hicham, M., Boivin, G., Guichard, A., Wyser-Rmili, C., Fournier, N., Mansouri, N., & Palma, M. D. (2025) · iScience · doi:10.1016/j.isci.2025.112498 · Cited by 13
“We further confirmed the presence of myeloid_MKI67 cells in a dataset collating hormone receptor-positive and triple-negative breast cancers from patients who received neoadjuvant therapy with anti-PD1 antibodies 46 (Figure 8G).”
Hu, X., Li, H., Chen, M., Qian, J., & Jiang, H. (2025) · Communications Biology · doi:10.1038/s42003-025-07947-7 · Cited by 15
Self-citationAtypical memory B cells acquire Breg phenotypes in hepatocellular carcinoma
Neo, S., Shuen, T. W. H., Khare, S., Chong, J., Lau, M., Shirgaonkar, N., Chua, L., Zhao, J., Lee, K., Tan, C., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.187025 · Cited by 15
“…cells in HCC was previously studied, we focused on the TNF + memory B cell subset that was also enriched for inflammatory pathways, sharing a distinct gene signature as a subset of B cells associated with immune tolerance from a different study cohort of patients receiving anti–PD-1 therapy (17).”
Liu, K., Han, H., Xiong, K., Zhai, S., Yang, X., Yu, X., Chen, B., Liu, M., Dong, Q., Meng, H., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05625-6 · Cited by 12
“To explore the impact of immune-checkpoint blockade (ICB) on metastatic epithelial cell subtypes, we collected single-cell data from patients receiving anti-PD1 (n = 29) and patients receiving anti-PD1 following neo-adjuvant chemotherapy (n = 11) [19].”
MethodKramer, G. F., Blair, T. C., Bambina, S., Kaur, A. P., Alice, A. F., Baird, J. R., Friedman, D., Dowdell, A. K., Tomura, M., Grassberger, C., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-62871-w · Cited by 16
“There is ongoing debate whether exhausted cells can recover to again participate in the tumor immune response, or whether these cells are terminally exhausted 44–48 .”
Zhang, H., Lu, X., Lu, B., Gullo, G., & Chen, L. (2024) · Future Oncology · doi:10.2217/fon-2023-0658 · Cited by 16
Yang, Y., Bo, S., Liang, L., Deng, K., Bai, L.-Y., Wang, T., Wang, Y.-S., Liu, K.-B., & Lu, C.-W. (2024) · ACS Nano · doi:10.1021/acsnano.3c10972 · Cited by 13
Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors
Wan, Z., Huang, J., Ou, X., Lou, S., Wan, J., & Shen, Z. (2024) · Anais Brasileiros de Dermatologia · doi:10.1016/j.abd.2023.09.003 · Cited by 14
Cd39 (Entpd1) in Tumors: A Potential Therapeutic Target and Prognostic Biomarker
Li, C., Zhang, L., Jin, Q., Jiang, H., & Wu, C. (2023) · Biomarkers in Medicine · doi:10.2217/bmm-2023-0202 · Cited by 13
Thakur, S., Haider, S. A., & Natrajan, R. (2023) · The Journal of Pathology · doi:10.1002/path.6158 · Cited by 13
“Together this highlights the heterogeneity in treatment response to anti-PD1 in BC [151].”
BackgroundHouse, I. G., Derrick, E. B., Sek, K., Chen, A. X. Y., Li, J., Lai, J., Todd, K. L., Munoz, I., Michie, J., Chan, C. W., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113014 · Cited by 15
Xia, Z., Lü, C., Pan, C., Li, J., Li, J., Mao, Y., Sun, L., & Jiang, H. (2023) · BMC Medicine · doi:10.1186/s12916-023-02960-1 · Cited by 19
“H and I CLTRP accurately predicted immunotherapy outcomes in the GSE177043 (H) and EGAD00001006608 (I) cohorts.”
MethodInfluentialLiu, Y., Fang, Y.-P., Bao, L.-L., Wu, F., Wang, S., & Hao, S. (2022) · Biomolecules · doi:10.3390/biom12101478 · Cited by 13
“Further, the marker genes EPCAM, CD24, CDH1, ACTA2, CDH2, and CD44 also confirmed the inferred trajectories (especially trajectory two) (Figure 4G,H and Figure S4).”
BackgroundMethodInfluentialWu, Y., Yu, S., & Qiao, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.990445 · Cited by 14
“Regardless of tumor subtype, T cells from breast cancer patients treated with anti-PD-1 were clonally expanded, mediated CD8+ T cell homing via CXCL13, and attracted CD4+ T cells by CXCR5 (Bassez et al., 2021).”
BackgroundGreenwald, N. F., Nederlof, I., Sowers, C., Ding, D. Y., Park, S., Kong, A., Houlahan, K. E., Varra, S. R., de Graaf, M., Geurts, V. C. M., et al. (2026) · Nature Cancer · doi:10.1038/s43018-026-01114-5 · Cited by 22
Cha, J., Kim, C. G., Sim, N. S., Kim, G., Son, W., Kim, D., Jung, Y., Hong, H. J., Lee, H. B., Kim, J., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102408 · Cited by 14
“35 In our HNSCC cohort, most patients showed significant clonal expansion after a single treat-ment cycle (Figure S5A).”
The untapped potential of radiation and immunotherapy for hormone receptor-positive breast cancer
Fenton, M., Yoneyama, M., Wennerberg, E., Lund, T., Tutt, A. N. J., Melcher, A. A., Demaria, S., & Somaiah, N. (2025) · npj Breast Cancer · doi:10.1038/s41523-025-00796-x · Cited by 13
“In response to pembrolizumab, expanding T-cells from HR + BCs expressed more genes associated with higher naivety compared to expandedT-cellsfromTNBC 155 , suggestingapotential roleforRTtoattract and activate functional cytotoxic T-cells within the TIME.”
Mebane, R. H., Noel, T., Ing, N., Gouin, K. H., Shah, A., Zitser, D., Martinez, A., Gupta, G. P., Demaria, S., Galluzzi, L., et al. (2025) · iScience · doi:10.1016/j.isci.2025.112808 · Cited by 12
“34,40,41 As this study focused on TLSs with a B cell core, we also performed a focused analysis comparing this lymphocyte population between infiltrated and non-infiltrated TNBCs.”
Li, S., Zhou, X., Feng, H., Huang, K., Chen, M., Lin, M., Lin, H., Deng, Z., Chen, Y., Liao, W., et al. (2025) · Cell Proliferation · doi:10.1111/cpr.70062 · Cited by 12
“…urothelial carcinoma (UC, GSE145281 [21]), triple negative breast cancer (TNBC, GSE169246 [22]), breast invasive carcinoma (BRCA, Bassez 2021 [23]), carcinoma of colon and rectum (CRC, GSE205506 [24]), non-small cell lung carcinoma (NSCLC, GSE207422 [25]) and basal cell carcinoma (BCC,…”
Yan, W., Shi, X., Zhao, Y., Liu, X., Jia, X., Gao, L., Yuan, J., Liao, A.-J., Yasui, H., Wang, X.-B., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-57966-5 · Cited by 12
“GZMB+ CD8 T cells kill cancer cells via cytotoxic mediators regulated by GZMB 18,19 .”
Tan, C., Huang, S., Xu, L., Zhang, T., Yuan, X., Li, Z., Chen, M., Chen, C., & Yan, Q. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02237-3 · Cited by 13
“ACP5 (Acid Phosphatase 5) encodes an iron-containing glycoprotein function [48, 49].”
BackgroundPKCα inhibitors promote breast cancer immune evasion by maintaining PD-L1 stability
Yu, J.-J., Xiang, Y., Gao, Y.-Z., Chang, S., Kong, R., Lv, X.-X., Yu, J.-M., Jin, Y., Li, C.-X., Ma, Y.-R., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.08.003 · Cited by 12
“Due to the higher mutational load, immunogenic TNBC is amenable to immunothera-peutic intervention and has a greater response rate to ICB than ER þ and HER2 þ breast cancer 23,24 .”
Okamura, K., Wang, L., Nagayama, S., Yamashita, M., Tate, T., Matsumoto, S., Takamatsu, M., Kitano, S., Kiyotani, K., & Nakamura, Y. (2024) · Oncoimmunology · doi:10.1080/2162402x.2024.2373530 · Cited by 12
“18 Several reports suggested possible immune suppressive function of granzyme K through an interaction with other immune cells, including macrophages.”
BackgroundMethodYang, J.-Y., Wang, C., Fu, D., Ho, L.-L., Galani, K., Chen, L., Frederick, D. T., He, L., Huang, A. Y., Robitschek, E. J., et al. (2024) · bioRxiv · doi:10.1101/2024.06.20.599945 · Cited by 12
“…effects, respectively 23 . mregDCs, transcriptionally characterized by single-cell studies 16,24,25 , were reported to be more abundant in responsive triple-negative breast cancer patients during anti-PD-1 treatment 26 , and they play an important role in mediating ICI effects in mouse models 27 .”
BackgroundSCIPAC: quantitative estimation of cell-phenotype associations
Gan, D., Zhu, Y., Lü, X., & Li, J. (2024) · Genome biology · doi:10.1186/s13059-024-03263-1 · Cited by 13
“Of these seven genes, at least five are supported by the literature: CCL4, XCL1, IFNG, and GZMB are associated with CD8 + T cell infiltration; they have been shown to have anti-tumor functions and are involved in cancer immunotherapy [41–43].”
BackgroundBossio, S., Abrate, C., Tosello, J., Rodríguez, C., Canale, F. P., Ramello, M. C., Brunotto, V., Richer, W., Rocha, D., Sedlik, C., et al. (2023) · OncoImmunology · doi:10.1080/2162402x.2023.2246319 · Cited by 18
“48 Further studies demonstrated that TNBC patients treated with paclitaxel in combination with anti-PD-1 showed an expansion of CXCL13 + T cells (CD4 + and CD8 + ) that expressed T cell exhaustion related genes.”
BackgroundXia, Z., Zhou, Y., Li, J., & He, J. (2022) · Cancers · doi:10.3390/cancers14225506 · Cited by 12
“To validate the predictive performance of RTM.Sig, three public gene expression datasets of ICT (respectively, accession number: EGAD00001006608, GSE111414, and GSE168204) were analyzed.”
MethodInfluentialMelanoma-intrinsic NR2F6 activity regulates antitumor immunity
Kim, H., Feng, Y.-M., Murad, R., Pozniak, J., Pelz, C., Chen, Y., Dalal, B., Sears, R., Sergienko, E., Jackson, M., et al. (2022) · bioRxiv · doi:10.1126/sciadv.adf6621 · Cited by 12
“The scRNA-seq data of human breast cancer (nonmetastatic primary invasive carcinoma) from 29 patients treated with one dose of anti – PD-1 ICT approximately 9 ± 2 days before surgery was previously report-ed ( 45 ).”
The origins of resident macrophages in mammary gland influence the tumorigenesis of breast cancer
Yang, Y., Hou, J., Liu, J., Bhushan, S., & Wu, G. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109047 · Cited by 14
SPICA: Swiss portal for immune cell analysis
Andreatta, M., David, F., Iseli, C., Guex, N., & Carmona, S. (2021) · Nucleic Acids Res. · doi:10.1093/nar/gkab1055 · Cited by 12
“(4) performed scRNA-seq on tumor biopsies from breast cancer patients, taken immediately before (pre-treatment) and after (on-treatment) receiving anti-PD1 immunotherapy.”
CellDrift: inferring perturbation responses in temporally sampled single-cell data
Jin, K., Schnell, D., Li, G., Salomonis, N., Prasath, V. B. S., Szczesniak, R., & Aronow, B. J. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac324 · Cited by 11
“Researchers have applied the technology in experiments with perturbation settings, such as diseases [4, 5], treatments [6, 7], genetic mutations [7, 8] and organ differentiation [9, 10], to explore transcriptional profiles across various biochemical states.”
Kamatani, T., Umeda, K., Iwasawa, T., Miya, F., Matsumoto, K., Mikami, S., Hara, K., Shimoda, M., Suzuki, Y., Nishino, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-63309-1 · Cited by 10
“Althoughobvioustumormicroenvironmentheterogeneityisobserved under immunotherapy 38 – 40 , little is known about whether differences in cellular clonality affect the phenotype of the tumor immune microenvironment.”
Gondal, M. N., Cieslik, M. P., & Chinnaiyan, A. M. (2025) · Scientific Data · doi:10.1038/s41597-025-04381-6 · Cited by 22
“27 study created a single-cell map, detailing intratumoral alterations occurring during anti-PD1 treatment in breast cancer patients (TNBC, HER2 + , ER + ).”
InfluentialZhang, T.-H., Zheng, Y., Xiang, H.-J., Chen, Y., & Wu, R. (2024) · Nano Today · doi:10.1016/j.nantod.2024.102453 · Cited by 11
Cho, N. W., Guldberg, S. M., Nabet, B., Yu, J.-Z., Kim, E. J., Hiam-Galvez, K. J., Yee, J. L., DeBarge, R., Tenvooren, I., Ashitey, N. A., et al. (2024) · bioRxiv · doi:10.1101/2022.09.20.508732 · Cited by 11
IFI30 as a key regulator of PDL1 immunotherapy prognosis in breast cancer.
Li, L., Fei, Y.-J., Dong, T., Song, Y.-X., Chen, X., Zhang, H.-D., Zhou, H., Liang, M., & Tang, J. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112093 · Cited by 11
Peng, Y., Yang, H., Chen, Q., Jin, H., Xue, Y., Du, M.-Q., Liu, S., & Yao, S.-Y. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-04965-7 · Cited by 11
“…CX3CR1, MIP-1β) [144–146, 149, 151, 153, 154, 157, 159–162, 165, 167, 168, 170, 172–174, 176, 177, 179, 181– 186, 188, 190, 191, 193–197, 199, 200, 205, 206, 209, 211, 212]; 3) transcription factors (Bcl-6, CDCA7, CTLA-4, CULT1, E2A, pERK1/2, granulysin, granzyme B, Helios, ICOS, Id2, ISGs,…”
ADGRE5-centered Tsurv model in T cells recognizes responders to neoadjuvant cancer immunotherapy
Li, J., Meng, Z., Cao, Z., Lü, W., Yang, Y., Li, Z., & Lü, S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1304183 · Cited by 11
Li, W., Lv, S., Liu, G., Lu, N., Jiang, Y., Hu, L., Xia, W., Xiang, Y., Xie, C., & He, J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1124066 · Cited by 10
“Previous studies have reported that elevated expression of cytotoxicity markers and inhibitory receptors in CD8 T cells is positively associated with potential clinical benefits of anti-PD-1 therapy (42).”
BackgroundJAML immunotherapy targets recently activated tumor-infiltrating CD8+ T cells
Eschweiler, S., Wang, A., Ramírez-Suástegui, C., Witzleben, A. V., Li, Y., Chee, S., Simon, H. A., Mondal, M., Ellis, M. J., Thomas, G. J., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112040 · Cited by 13
“…cluster also expressed high levels of other transcripts linked to exhaustion ( Lag3 , Havcr2 , Tox ) (Figures 5B–5G), and in agreement with previous studies, 30,31 these results indicate that expression of these exhaustion-like markers in murine TILs is unlikely to impede their functionality.”
Koh, S., & Ellisen, L. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.11.001 · Cited by 11
Sun, Y., Jiang, L., Wen, T., Guo, X., Shao, X., Qu, H., Chen, X., Song, Y., Wang, F., Qu, X., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.670900 · Cited by 13
“…with anti-PD1/PDL1 therapy to figure out the changes of cell subsets after treatments and differences between responders and non-responders, which could contribute to predict prognosis, select suitable therapy strategy and monitor the condition of diseases (Bassez et al., 2021; Gohil et al., 2021).”
BackgroundFu, Y., Li, M., Wu, S., Wang, J., & Wang, S. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08685-2 · Cited by 11
“Across NSCLC and BC, higher TREM2 ⁺ macrophage abundance inversely correlates with cytotoxic CD8 ⁺ T cell in fi ltration and response to PD-1/PD-L1 blockade [124 – 126].”
Wang, R., Zhang, Y.-Y., Meng, X., Zhao, J.-L., Xing, Y., Ouyang, Q., Zhang, N., Chen, H.-P., Miao, N.-Y., Song, E.-W., et al. (2025) · Advancement of science · doi:10.1002/advs.202506518 · Cited by 10
Decoding tumor heterogeneity: A spatially informed pan-cancer analysis of the tumor microenvironment
Lodi, F., Vanmassenhove, S., Chen, D., Boeckx, B., Maciel, L. F., Peeters, F., Donders, E., Song, H., Harbers, L., Poźniak, J., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102416 · Cited by 10
“11,74 We additionally regressed out for the hypoxia signature 74 when subclustering macrophages/monocytes and Bcells to avoid the formation of subtypes driven by hypoxia.”
Self-citationDo, C., & Lähdesmäki, H. (2025) · Bioinform. · doi:10.1093/bioinformatics/btaf241 · Cited by 10
“We are using pre-treatment samples from three studies (Bassez et al. 2021, Alvarez-Breckenridge et al. 2022, Pozniak et al. 2024) and two cancer types (melanoma and breast cancer) with different subtypes.”
Xu, J., Zhou, H., Liu, Z., Huang, Y., Zhang, Z., Zou, H., & Wang, Y. (2025) · Scientific Reports · doi:10.1038/s41598-025-97667-z · Cited by 8
“Notably, recent advances in single-cell RNA sequencing have greatly improved our understanding of the tumor immune microenvironment in a wide range of cancers, including hepatocellular carcinoma 12 , breast cancer 13 , lung cancer 14 and renal cancer 15 .”
Guo, Y., Wan, R., Duan, J., Yuan, L., Wang, Z.-J., Zhong, J., Zhang, X., Ma, Z., Bai, H., & Wang, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02190-2 · Cited by 10
“15 We fi rst compared the transcriptomes of paired pretreatment versus on-treatment samples and nonresponders versus responders in GSE91061; we also compared the transcriptomes of pretreatment versus on-treatment tumor cells in EGAS00001004809.”
A highly resolved integrated single-cell atlas of human breast cancers
Chen, A., Kroehling, L., Ennis, C. S., Denis, G. V., & Monti, S. (2026) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqaf217 · Cited by 9
Liu, M.-D., Qian, M., Sun, W., Sun, X., Sun, Y., Yu, M.-X., Tang, X.-Y., Mao, X., Sun, C., Qi, Q., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010871 · Cited by 10
Li, L.-H., Jiang, R.-T., Yu, J.-F., & Li, M. (2024) · Small · doi:10.1002/smll.202409154 · Cited by 10
Sun, C., & Liu, Z.-P. (2024) · Comput. Methods Programs Biomed. · doi:10.1016/j.cmpb.2024.108481 · Cited by 10
Immune microenvironment dynamics of HER2 overexpressing breast cancer under dual anti-HER2 blockade
Batalha, S., Gomes, C. M., & Brito, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1267621 · Cited by 13
Kumar, R., Dhaka, B., Sahoo, S., Jolly, M., & Sabarinathan, R. (2023) · bioRxiv · doi:10.1002/1878-0261.13443 · Cited by 10
“for the exhausted T-cell for which we considered three genes (LAG3, HAVCR2, PDCD1) from (36,49).”
BackgroundResultXie, L., Ning, Z., Hua, Y., Wang, P., & Meng, Z. (2023) · Hepatology Communications · doi:10.1097/hc9.0000000000000131 · Cited by 10
“[40] This phenomenon may be explained by the intrinsic nature of cancer.”
Yuan, L.-L., Chen, Z., Qin, J., Qin, C., Bian, J., Dong, R.-F., Yuan, T., Yiting, X., Kong, L., & Xia, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1019870 · Cited by 11
Shen, R., Li, P., Zhang, B., Feng, L., & Cheng, S. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03661-8 · Cited by 16
Li, Y., Zang, Y., Fan, T., Li, Z., Li, A., Lv, W., Wang, Q., Li, Q., Li, Y., Li, Q., et al. (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.05.019 · Cited by 11
“could promote progression-free and overall survival [1,2,7,57,58].”
BackgroundShi, H., Zhang, X., Yang, Z., Dong, J., Wang, Y., Zhou, Y., Li, X., Guo, C., & Hu, Z. (2022) · Oncogene · doi:10.1038/s41388-022-02478-5 · Cited by 13
Zhang, Y., Tong, G.-H., Wei, X., Chen, H., Liang, T.-J., Tang, H., Wu, C.-A., Wen, G.-M., Yang, W.-K., Liang, L., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2021.723477 · Cited by 10
“The expression of cytotoxicity genes CD8A, CD8B, GZMA, GZMB and PRF1 can represent immune cell cytotoxicity (Huson et al., 2016; Mitchell et al., 2020) (Balint et al., 2020; Bassez et al., 2021).”
BackgroundEcotypes of triple-negative breast cancer in response to chemotherapy
Yan, Y., Lin, Y., Kumar, T., Bai, S., Thennavan, A., Li, J., Sei, E., Tran, T. M., Hu, M., Rao, M., et al. (2026) · Nature · doi:10.1038/s41586-026-10469-9 · Cited by 14
Smart responsive hydrogels combined with AI design for tumor therapy
Wang, Q., Li, J., Feng, N., & Zhang, Y. (2026) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2026.02.019 · Cited by 7
“To overcome the immunosuppressive TMEt, researchers have encapsulated various immune adjuvants in hydrogels to enhance cross-presentation of antigens and thereby promote immune cell infiltration into tumors 263,264 .”
Zhao, Q., Huang, R., Wang, C., Hu, J., Nie, R. C., Jian, R., Wang, Y., Wang, D., Liang, C., Chen, Y., et al. (2026) · Cancer Cell · doi:10.1016/j.ccell.2026.01.015 · Cited by 10
DC subsets and states unraveled across human juxtatumoral and malignant tissues
Mulder, K., Gardet, M., Kong, W. T., Patel, A. A., Calvez, A., Gessain, G., de la Calle‐Fabregat, C., Piot, C., Blampey, Q., Poupaud, E., et al. (2025) · Nature Immunology · doi:10.1038/s41590-025-02337-x · Cited by 12
“While extending the expansion of CCR7 mDCs and DC3s in multiple cancers 18,23 , we functionally observed that CCR7 + DC1s displayed elevated levels of IL-12 and costimulatory molecules, reinforcing their role as activated DCs 49 .”
InfluentialZhao, X., Qin, X., Wang, R., Wang, Y., He, Y., Wang, Y., Li, K., Zhang, P., Yang, C., Wang, M., et al. (2025) · Advanced Materials · doi:10.1002/adma.202502800 · Cited by 9
CDK12/13 inactivation triggers STING-mediated antitumor immunity in preclinical models
Bao, Y., Chang, Y., Tien, J. C.-Y., Cruz, G., Yang, F., Mannan, R., Mahapatra, S., Paturu, R., Cao, X., Su, F., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci193745 · Cited by 13
“Additionally, investigations have extended to breast cancer subtypes (79) like triple-negative, HER2-positive, and estrogen receptor (ER)–positive, as well as kidney cancer, specifically clear cell renal carcinoma (80), and liver cancers (81) such as hepatocellular carcinoma and intrahepatic…”
Jagged1 regulates extracellular matrix deposition and remodeling in triple-negative breast cancerPreprint
Parikainen, M., Suwal, U., Rappu, P., Heino, J., & Sahlgren, C. (2025) · bioRxiv · doi:10.1101/2025.05.23.655829 · Cited by 9
“Using previously published single-cell RNA sequencing (scRNA-seq) data 27 , publicly available breast cancer patient data 28 , and a 3D in vitro model, we demonstrate that Jagged1 enhances invasiveness, cancer stem cell-like (CSC) features, and expression of ECM-related genes in TNBC cells.”
InfluentialTwo chemotherapeutic agents expand stem-like CD62L+CD8+ T cells in antitumor immune responses
Ruan, X., Wu, L., Tang, Z., Li, Y., Wang, J., Jiang, H., Zhang, L., Wang, S., Chen, Z., Yuan, C., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1533857 · Cited by 10
The impact of glucocorticoid receptor transactivation on context-dependent cell migration dynamics
Pósa, S. P., Saskői, É., Bársony, L., Pongor, L., Fekete, F., Papp, J., Bozsik, A., Patócs, A., & Butz, H. (2025) · Scientific Reports · doi:10.1038/s41598-025-88666-1 · Cited by 9
Single-cell technology for drug discovery and development
Zhang, A., Zou, J., Xi, Y., Gao, L., Deng, F., Liu, Y., Gao, P., Tong, H. H. Y., Tan, L., Zou, X., et al. (2024) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2024.1459962 · Cited by 9
Jiang, Y., Bei, W.-X., Li, W., Huang, Y., He, S., Zhu, X., Zheng, L., Xia, W., Dong, S., Liu, Q., et al. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.70061 · Cited by 10
“81 However, prevention or reversion of the CD8 + T cells’ exhaustion status and restoration of its cytotoxic status was critical for improving the ICB anti-tumoral efficacy.”
BackgroundNonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology
DeWitt, J. T., Raghunathan, M., & Haricharan, S. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.10.001 · Cited by 10
Ye, D., Zhou, S. Y., Dai, X., Xu, H., Tang, Q., Huang, H., & Bi, F. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189161 · Cited by 8
Liu, H., Sima, X., Xiao, B., Gulizeba, H., Zhao, S., Zhou, T., & Huang, Y. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05123-9 · Cited by 9
“Breast cancer (BRCA) scRNA-seq data [20] were downloaded from lambrechtslab data access (vib.be) for external validation.”
MethodYan, H., Huang, J., Li, Y., & Zhao, B. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00598-z · Cited by 11
“6F) [42], GSE123814 (basal or squamous cell cancer; responders vs. non-responders, 3 vs. 5; Fig.”
The interplay between eosinophils and T cells in breast cancer immunotherapy
Zerdes, I., Matikas, A., & Foukakis, T. (2023) · Molecular Oncology · doi:10.1002/1878-0261.13413 · Cited by 9
Massa, D., Tosi, A., Rosato, A., Guarneri, V., & Dieci, M. V. (2022) · Cancers · doi:10.3390/cancers14194885 · Cited by 17
Zhao, J., Dong, Y., Zhang, Y., Wang, J., & Wang, Z. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114585 · Cited by 12
TCR sequencing in cancer immunology and immunotherapy: what, when, where, why, and how
Nose, Y., Figueiredo, I., Tuballes, K., Valle, D. M. D., Gonsalves, T. R., Guo, R., Ioannou, G., Cabal, R., Gonzalez‐Kozlova, E., & Gnjatic, S. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-013499 · Cited by 9
Zhang, Y., Du, Y., Wang, J., Wang, D., Li, J., Zhang, J., Zhao, Y., Sun, S., Sun, H., Qi, J., et al. (2026) · Gastroenterology · doi:10.1053/j.gastro.2025.09.043 · Cited by 10
Estrogen receptor signaling drives immune evasion and immunotherapy resistance in HR+ breast cancer
Palomeque, J. Á., Serra-Mir, G., Blasco-Benito, S., Brunel, H., Torren-Duran, P., Pérez-Núñez, I., Cannatá, C., Comerma, L., Menéndez, S., Servitja, S., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci193153 · Cited by 8
“To further analyze ER α signaling dynamics during therapy-mediated immune pressure, we evaluated the estrogen response using single-cell RNA-Seq available data from patients with HR + BC before (pretreatment) and during (on-treatment) therapy consisting of 1 cycle of anti–PD-1 treatment (42).”
Zhou, L.-J., Liu, M., Liu, F., Wang, Z., Li, X., Peng, X., Ma, W., Guo, P., Yuan, L., Wołczyński, S., et al. (2025) · Oncogene · doi:10.1038/s41388-025-03627-2 · Cited by 9
Next-generation sequencing in breast cancer: current clinical applications and future directions
Zuhdi, N. F. M., Siddig, A., Nafi, S. N. M., Salleh, M. M., Yahya, M. M., Zain, W. Z. W., Din, T. A. T. T., & Rahman, W. F. W. A. (2025) · Annals medicus · doi:10.1080/07853890.2025.2569989 · Cited by 8
“This finding may shed light on the heterogeneity of tumour cells in response to immunotherapy [72]. scRNA-seq is a potential discovery tool that offers a comprehensive understanding of breast cancer heterogeneity, enabling the exploration of the mechanisms of metastasis and drug resistance.”
Young, J., Inamo, J., Caterer, Z., Krishna, R., & Zhang, F. (2025) · Advancement of science · doi:10.1002/advs.202503289 · Cited by 8
Wang, Q., Li, S., Wu, Y., Yu, X., Dai, Y., Wang, Y., Li, L., Yang, M., Lin, K., Shao, W., et al. (2025) · Research · doi:10.34133/research.0915 · Cited by 7
“Cells were colored by cell types defined in a breast cancer scRNA-seq dataset [65] (left) and by MDSC types predicted using the scPred package [70] (right).”
InfluentialLu, C., Liang, L., Wu, Y., Yang, Y., Poschel, D. B., Zhao, Y., Pei, L., Yu, M., Zoccheddu, M., Bombin, S., et al. (2025) · Oncogene · doi:10.1038/s41388-025-03543-5 · Cited by 8
“M Quanti fi cation of indicated immune cells as in ( L ). treated with pembrolizumab [28], PD-1 and FasL expression levels are higher in tumor-in fi ltrating T cells in responders than in non-responders (Fig.”
Breast cancer organoids: Advancements and applications in precision medicine
Leung, D. T. H., Kaur, J., Richardson, G. E., & Jardé, T. (2025) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2025.104914 · Cited by 7
PD-1 regulates tumor-infiltrating CD8+ T cells in both a cell-intrinsic and a cell-extrinsic fashion
Pauken, K. E., Markson, S. C., Conway, T. S., Juneja, V. R., Shahid, O., Burke, K. P., Rowe, J. H., Nguyen, T. H., Collier, J. L., Walsh, J. M. L., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20230542 · Cited by 6
AAnet Resolves a Continuum of Spatially Localized Cell States to Unveil Intratumoral Heterogeneity
Venkat, A., Youlten, S. E., Juan, B. P. S., Purcell, C. A., Gupta, S., Amodio, M., Neumann, D., Lock, J. G., Westacott, A. E., McCool, C. S., et al. (2025) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-0684 · Cited by 9
“After stringent filtering, we retained 15 samples from Pal and colleagues (52), nine from Wu and colleagues (54), eight from Bassez and colleagues (53), and two patient-derived xenograft (PDX) samples.”
Wu, S.-X., Jiang, B.-H., Li, Z.-M., Tang, Y., Luo, L.-Q., Feng, W., Jiang, Y.-L., Tan, Y.-R., & Li, Y.-H. (2025) · Breast Cancer Research · doi:10.1186/s13058-025-01980-4 · Cited by 8
“Additionally, research by Bassez et al. suggested that macrophage PD-L1 expression may further influence T cell function through immune checkpoint inhibition pathways [83].”
Wang, R., Yan, Q., Guo, X., Song, F., Xiong, Z., Cai, S., Bian, X., Wong, M. H., Cao, Q., Cheng, L., et al. (2025) · Genome Medicine · doi:10.1186/s13073-025-01441-9 · Cited by 7
“Module III represents CAFs expressing COL1A1, COL1A2, and COL3A1 [35] enriched in the cancer regions, whereas module IV identifies a subset known as myofibroblasts (myCAFs) (COL12A1, THBS2) that mainly contribute to extracellular matrix remodeling and growth and metastasis of cancer cells [85, 86].”
Metoikidou, C., Карнаухов, В. К., Boeckx, B., Timperi, E., Bonté, P., Wang, L., Espenel, M., Albaud, B., Loirat, D., Wang, X., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.101973 · Cited by 7
“Similar findings in early-stage BC 25 suggest that the presence of tissue-resident exhausted CD8 + T cells correlates with clinical responses to aPD-1 therapy.”
Self-citation
Metadata
- 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
- 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
- green
- lirias.kuleuven.be
- Licence
- 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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