Cited by 389Pancreatic and Hepatic Oncology ResearchTGF-β signaling in diseasesCancer Immunotherapy and Biomarkers

The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.

Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis

Open access

Zhang, Yaqing, Lazarus, Jenny, Steele, Nina G., Yan, Wei, Lee, Ho-Joon, Nwosu, Zeribe C., Halbrook, Christopher J., Menjivar, Rosa E., Kemp, Samantha B., Sirihorachai, Veerin R., Velez-Delgado, Ashley, Donahue, Katelyn, Carpenter, Eileen S., Brown, Kristee L., Irizarry-Negron, Valerie, Nevison, Anna C., Vinta, Alekya, Anderson, Michelle A., Crawford, Howard C., Lyssiotis, Costas A., Frankel, Timothy L., Bednar, Filip, Pasca di Magliano, Marina·2020·Cancer Discovery

DOI 10.1158/2159-8290.cd-19-0958PMC PMC7224338

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to the immunosuppressive microenvironment, we depleted Tregs in a mouse model of pancreatic cancer. Contrary to our expectations, Treg depletion failed to relieve immunosuppression and led to accelerated tumor progression. We show that Tregs are a key source of TGFβ ligands and, accordingly, their depletion reprogramed the fibroblast population, with loss of tumor-restraining, smooth muscle actin–expressing fibroblasts. Conversely, we observed an increase in chemokines Ccl3, Ccl6, and Ccl8 leading to increased myeloid cell recruitment, restoration of immune suppression, and promotion of carcinogenesis, an effect that was inhibited by blockade of the common CCL3/6/8 receptor CCR1. Further, Treg depletion unleashed pathologic CD4+ T-cell responses. Our data point to new mechanisms regulating fibroblast differentiation in pancreatic cancer and support the notion that fibroblasts are a heterogeneous population with different and opposing functions in pancreatic carcinogenesis. Significance: Here, we describe an unexpected cross-talk between Tregs and fibroblasts in pancreatic cancer. Treg depletion resulted in differentiation of inflammatory fibroblast subsets, in turn driving infiltration of myeloid cells through CCR1, thus uncovering a potentially new therapeutic approach to relieve immunosuppression in pancreatic cancer. See related commentary by Aykut et al., p. 345. This article is highlighted in the In This Issue feature, p. 327

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1158/2159-8290.cd-19-0958

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Cancer statistics, 2018
Siegel, R. L., Miller, K. D., & Jemal, A. (2018) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21442 · Cited by 16,632
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Öhlund, D., Handly-Santana, A., Biffi, G., Elyada, E., Almeida, A. S., Ponz-Sarvise, M., Corbo, V., Oni, T. E., Hearn, S. A., Lee, E. J., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162024 · Cited by 2,590
FOXP3+ regulatory T cells in the human immune system
Sakaguchi, S., Miyara, M., Costantino, C. M., & Hafler, D. A. (2010) · Nature reviews. Immunology · doi:10.1038/nri2785 · Cited by 2,524
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471
Self-citation
Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts
Elyada, E., Bolisetty, M., Laise, P., Flynn, W. F., Courtois, E. T., Burkhart, R. A., Teinor, J. A., Belleau, P., Biffi, G., Lucito, M. S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0094 · Cited by 2,241
Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma
Provenzano, P. P., Cuevas, C., Chang, A. E., Goel, V. K., Von Hoff, D. D., & Hingorani, S. R. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.01.007 · Cited by 2,195

Show all 73 references

Sorted by citations

Items 301–389 of 389

Integrative multi-omics reveal a CD4⁺ T cell–derived six-gene signature linking the immune–stromal ecosystem to prognosis and immunotherapy selection in pancreatic cancer
Liang, Y., Shuoshuo, M. A., Chen, X., Su, Y., Zhong, D., Yan, H., Chen, Y., Wang, M., Leng, Z., & Huang, X. (2026) · BMC Cancer · doi:10.1186/s12885-026-15613-2 · Cited by 1
Regulatory elements in the Sox9 locus license the initiation of pancreatic ductal adenocarcinoma
Ballester, M., Kurilla, A., Dai, Y., Bergara-Muguruza, L., Radke, K., Maurer, H. C., Espinet, E., Høj, K., Marisch-Delgado, A., Seymour, P. A., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117176 · Cited by 2
Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From Multidatabase Analysis
Kumar, V., Khan, N. H., Kumar, S. N., Mahajan, N., Aziz, W., Kumar, V., & Verma, C. (2026) · Biochemistry Research International · doi:10.1155/bri/6647501 · Cited by 1
T reg cells promote immunotherapy-induced immune evasion by restraining CD4 T cell control of MHC-I–deficient metastatic pancreatic cancer
Schmiechen, Z. C., Cruz-Hinojoza, E., Hilk, A. L., Ellefson, M. A., Tsai, A. K., Dres, O. M., Kang, L., Geuenich, M. J., Butler, J. Z., Burrack, A. L., et al. (2026) · Science Immunology · doi:10.1126/sciimmunol.adz4302 · Cited by 1
APE1/Ref-1: multifunctional biology, selective inhibition, and the path to clinical translation
Moerland, J. A., Gampala, S., Fishel, M. L., & Kelley, M. R. (2026) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2026.2706465 · Cited by 1
Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases
Chen, Y., Shi, Y., & You, J. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02910-2 · Cited by 1
The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8+ T Cell-Orientated Therapy
Hung, Y., Chen, L., & Hung, W. (2022) · Biomedicines · doi:10.3390/biomedicines10040926 · Cited by 1
Exploration of immune cell heterogeneity by single‐cell RNA sequencing and identification of secretory leukocyte protease inhibitor as an oncogene in pancreatic cancer
Ai, B., Liang, Y., Yan, T., & Lei, Y. (2024) · Environmental Toxicology · doi:10.1002/tox.24200 · Cited by 1
Comprehensive analysis of prognostic immune‑related genes associated with the tumor microenvironment of pancreatic ductal adenocarcinoma
Yan, S.-B., Fang, J., Zhu, Y., Xie, Y., & Fang, F. (2020) · Oncology Letters · doi:10.3892/ol.2020.12228 · Cited by 1
Tissue Infiltrating Immune Cells and Endometrial Cancer Prognosis
Drakes, M. L., Drakes, M. L., Mehrotra, S., Potkul, R. K., Czerlanis, C. M., & Stiff, P. J. (2021) · Clinical Oncology and Research · doi:10.31487/j.cor.2021.04.01 · Cited by 1
The Effects of Treatment on Peripheral Blood Immune Cell Profile in Pancreatic Ductal Adenocarcinoma (PDAC)
Tulytė, S., Characiejus, D., Matuzevičienė, R., Janiulionienė, A., Radzevičius, M., Žvirblis, T., & Šileikis, A. (2022) · Anticancer Research · doi:10.21873/anticanres.15794 · Cited by 1
Activated regulatory T-cells, dysfunctional and senescent T-cells dominate the microenvironment of pancreatic cancerPreprint
Sivakumar, S., Abu‐Shah, E., Ahern, D., Arbe-Barnes, E. H., Mangal, N., Reddy, S., Rendek, A., Easton, A., Kurz, E., Silva, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.20.163071 · Cited by 1
The Prognostic Value of Tumor-Infiltrating Immune Cells in Gynecologic CancersPreprint
Chen, W., Hu, T., & He, C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.01.31.429066 · Cited by 1
Multi-dimensional analyses identify genes of high priority for pancreatic cancer researchPreprint
Nwosu, Z. C., Giza, H., Nassif, M., Charlestin, V., Menjivar, R. E., Kim, D., Kemp, S. B., Steele, N. G., Hu, J., Hu, B., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.28.446056 · Cited by 1
Self-citation
Tissue-resident regulatory T cells exert dualistic anti-tumour and pro-repair function in the exocrine pancreasPreprint
Stockis, J., Yip, T., Raghunathan, S., Garcia, C., Lee, S., Simpson, C., Silvain, S., Schuijs, M. J., Araos, J., Png, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.15.580302 · Cited by 1
Spatial Biology and Organoid Technologies Reveal a Potential Therapy-Resistant Cancer Stem Cell Population in Pancreatic Ductal AdenocarcinomaPreprint
Adhikary, P., Chakrabarti, J. L., Mallick, S., Sun, X., Ezuma-Igwe, U., Branch, A. G., Wang, J., Braissand, N., Corbett, M. P., Kim, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.22.655586 · Cited by 2
Immune Selection Pressure Contributes to Pancreatic Cancer Immune EvasionPreprint
Ajina, R., Zuo, A., Wang, S., Moussa, M., Cooper, C. J., Shen, Y. L., Johnson, Q. R., Parks, J. M., Smith, J. C., Catálfamo, M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.15.151274
Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancerPreprint
Fan, X., & He, C. (2021) · medRxiv · doi:10.1101/2021.08.24.21262578
Essays on the value of accounting disclosure on capital markets
Platikanova, P. (2010) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Comprehensive Analysis of the Immunogeomic Landscape and Clinical Features in Cervical Cancer
Fan, X., & He, C. (2021) · International Conference on Computational Biology and Bioinformatics (ICCBB) · doi:10.1145/3512452.3512457
The MLL3/TP53/PIK3CA cancer driver mutations promote HIF1α-dependent recruitment and differentiation of pro-tumor ICOS hi GITR hi Blimp-1 + effector regulatory T cells in breast tumorsPreprint
Boutet, M., Nishitani, K., Erler, P., Couturier, N., Zhang, Z., Militello, A. M., de Miranda, M. C., Barbieux, E., Guillen, E., Suzuki, M., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.02.510540
The Prospects of Immunotherapy in Pancreatic Cancer
Ying, H., & Yao, W. (2022) · Springer eBooks · doi:10.1007/978-3-031-05724-3_22
Data from Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer
Gupta, V. K., Sharma, N., Durden, B. C., Garrido, V. T., Kesh, K., Edwards, D., Wang, D., Myer, C., Mateo-Victoriano, B., Kollala, S. S., et al. (2023) · doi:10.1158/0008-5472.c.6513001.v1
Data from Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions
Carpenter, E. S., Elhossiny, A. M., Kadiyala, P., Li, J., McGue, J. J., Griffith, B. D., Zhang, Y., Edwards, J., Nelson, S., Lima, F., et al. (2023) · doi:10.1158/2159-8290.c.6651113.v1
Self-citation
Data from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Heiduk, M., Klimová, A., Reiche, C., Digomann, D., Beer, C., Aust, D. E., Distler, M., Weitz, J., Seifert, A. M., & Seifert, L. (2023) · doi:10.1158/1078-0432.c.6675230.v1
Data from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Heiduk, M., Klimová, A., Reiche, C., Digomann, D., Beer, C., Aust, D. E., Distler, M., Weitz, J., Seifert, A. M., & Seifert, L. (2023) · doi:10.1158/1078-0432.c.6675230
Pancreatic Neoplasms Are Frighteningly Common: A Role for Immune Surveillance?
Hoffman, M. T., & Dougan, S. K. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0332
Data from Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions
Carpenter, E. S., Elhossiny, A. M., Kadiyala, P., Li, J., McGue, J. J., Griffith, B. D., Zhang, Y., Edwards, J., Nelson, S., Lima, F., et al. (2023) · doi:10.1158/2159-8290.c.6651113
Self-citation
Interactions in the Local Onco-Sphere: An Overview
Saw, P. E., & Song, E. (2023) · Springer eBooks · doi:10.1007/978-981-99-1183-7_2
Correlation between PRSS23 and Prognosis and Immune Regulation in Pancreatic CancerPreprint
wang, J., & deng, Z. (2023) · Research Square · doi:10.21203/rs.3.rs-3263273/v1
Immunotherapy in Pancreatic Cancer
Yeung, Z. P., & Kundranda, M. N. (2023) · Springer eBooks · doi:10.1007/978-3-031-38623-7_6
Chemokine expression profiles predict overall survival and immune infiltration in patients with pancreatic adenocarcinoma
Peng, X., Lv, S., Fan, Y., Zhang, J., Liu, H., Liu, Y., & Feng, W. (2023) · Journal of Pancreatology · doi:10.1097/jp9.0000000000000164
prognostic values of BOLA family members and correlated with immune infiltrates in Pancreatic adenocarcinomaPreprint
Long, Q., & Fan, Y. (2024) · Research Square · doi:10.21203/rs.3.rs-3852177/v1
Investigating the Causal Relationship between Immune Cell Phenotypes and Pancreatic Cancer Risk: A Mendelian Randomization StudyPreprint
Chai, W., Huang, K., Li, J., Guo, F., Wu, Y., & Liu, J. (2024) · Research Square · doi:10.21203/rs.3.rs-4002089/v1
Current Status and Perspectives of Pancreatic Cancer Tumor Microenvironment and Therapy
Guo, X. (2024) · International Journal of Frontiers in Medicine · doi:10.25236/ijfm.2024.060206
Regulatory T-cells in pancreatic cancer
Merchant, N., Malla, R. R., & Nagaraju, G. P. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23523-8.00023-7
A Case of Five-Year Survival in Metastatic Pancreatic Cancer
Park, H. J., Lee, K. H., Lee, J. K., Lee, K. T., Choi, Y. H., & Park, J. K. (2024) · The Korean Journal of Pancreas and Biliary Tract · doi:10.15279/kpba.2024.29.3.110
Construction and Validation of a Novel T/NK-Cell Prognostic Signature for Pancreatic Cancer Based on Single-Cell RNA Sequencing
Wang, Y., Zhang, C., Zhang, J., Huang, H., & Guo, J. (2024) · Cancer Investigation · doi:10.1080/07357907.2024.2424328
Causal role of 731 immune cells in pancreatic cancer: a Mendelian randomization study
Feng, Z., Cao, R., Wu, J., Mo, J., Wang, Q., Wu, S., Ma, Q., Wang, Z., Zhou, C., & Wu, Z. (2025) · Journal of Pancreatology · doi:10.1097/jp9.0000000000000212
Cytokine-based immunotherapy in pancreatic cancer
Gordo-Ortiz, A., Ortiz-de-Solórzano, I., & Navarro, F. C. (2025) · International review of cytology · doi:10.1016/bs.ircmb.2025.03.001
Programmed cell death protein-1 and other inhibitory receptors expressed by regulatory T cells as a restraining factor of checkpoint therapy
Васильевич, Б. Е., Ostanin, A., & Chernykh, E. R. (2025) · Archive of oncology · doi:10.2298/aoo241217003b
Regulatory elements of pancreas development license the initiation of pancreatic ductal adenocarcinomaPreprint
Ballester, M., Kurilla, A., Dai, Y., Maurer, H. C., Espinet, E., Høj, K., Delgado, A. M., Seymour, P. A., Omar, S., Rift, C. V., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.06.658264
T Cell-Antigen Presenting Cell Communication: Immunological Synapses, Kinapses and Villiapses
Dustin, M. L. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00162-9
Peculiarities of inhibitory receptor expression on effector and regulatory T cells in the context of immune checkpoint inhibitor therapy
Васильевич, Б. Е., Vasilchenko, P. V., & Chernykh, E. R. (2025) · Сибирский научный медицинский журнал · doi:10.18699/ssmj20250503
Epithelial FOXP3 Drives Pancreatic Fibrosis through O-glycosylated IL-6Preprint
Gong, R., Ren, M., Wang, J., Zhang, W., Ping, S., Lei, K., Yu, Q., Ma, L., Gao, C., Zhao, C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.19.689208
Taurine-Modified Gossypol Exerts Dual Anti-Hepatocellular Carcinoma Effects by Inactivating PI3K/AKT Pathway and Targeting FASN-Mediated Lipid Metabolism in Regulatory T Cells
He, W., Shi, J., Deng, G., Liu, W., Kou, L., Hu, J., Lin, Y., Lin, X., Sheng, J., & Wu, F. (2025) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s572305
Additional file 2 of Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine
Miao, S.-N., Chai, M.-Q., Liu, X.-Y., Wei, C.-Y., Zhang, C.-C., Sun, N.-N., Fei, Q.-Z., Peng, L.-L., & Qiu, H. (2024) · Figshare · doi:10.6084/m9.figshare.25609270
Additional file 8 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986721
Additional file 9 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986724
Additional file 6 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986712
Additional file 4 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986703
Additional file 1 of singleCellBase: a high-quality manually curated database of cell markers for single cell annotation across multiple species
Meng, F.-L., Huang, X.-L., Qin, W.-Y., Liu, K.-B., Wang, Y., Li, M., Ren, Y.-H., Li, Y.-Z., & Sun, Y.-M. (2023) · Figshare · doi:10.6084/m9.figshare.24172153
Additional file 3 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986697
Additional file 1 of Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine
Miao, S.-N., Chai, M.-Q., Liu, X.-Y., Wei, C.-Y., Zhang, C.-C., Sun, N.-N., Fei, Q.-Z., Peng, L.-L., & Qiu, H. (2024) · Figshare · doi:10.6084/m9.figshare.25608795
Additional file 4 of Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine
Miao, S.-N., Chai, M.-Q., Liu, X.-Y., Wei, C.-Y., Zhang, C.-C., Sun, N.-N., Fei, Q.-Z., Peng, L.-L., & Qiu, H. (2024) · Figshare · doi:10.6084/m9.figshare.26706990
Molecular and spatiotemporal characterization of cells in murine atherosclerotic plaquesPreprint
Hou, P., Liu, Z., Fang, J., Wang, Z., Liu, S., Wang, S., Melino, G., Li, P., Shi, Y., & Shao, C. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.04.611323
Additional file 3 of Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine
Miao, S.-N., Chai, M.-Q., Liu, X.-Y., Wei, C.-Y., Zhang, C.-C., Sun, N.-N., Fei, Q.-Z., Peng, L.-L., & Qiu, H. (2024) · Figshare · doi:10.6084/m9.figshare.26706987
Additional file 1 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986688
Additional file 5 of Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine
Miao, S.-N., Chai, M.-Q., Liu, X.-Y., Wei, C.-Y., Zhang, C.-C., Sun, N.-N., Fei, Q.-Z., Peng, L.-L., & Qiu, H. (2024) · Figshare · doi:10.6084/m9.figshare.26706993
Additional file 2 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986694
Additional file 7 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986715
Additional file 5 of Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
Kiryu, S., Ito, Z., Suka, M., Bito, T., Kan, S., Uchiyama, K., Saruta, M., Hata, T., Takano, Y., Fujioka, S., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16986706
Additional file 6 of Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine
Miao, S.-N., Chai, M.-Q., Liu, X.-Y., Wei, C.-Y., Zhang, C.-C., Sun, N.-N., Fei, Q.-Z., Peng, L.-L., & Qiu, H. (2024) · Figshare · doi:10.6084/m9.figshare.26706996
A bispecific ADC against CCR8 and TNFR2 elicits potent antitumor efficacy
Li, W., Li, Q., Zhou, Q., Wu, Y., Wang, M.-W., & Ying, T. (2025) · Medicine in Drug Discovery · doi:10.1016/j.medidd.2025.100226
Myeloid–Treg Crosstalk Disruption by Photochemical Activation and Immune Checkpoint Therapy Triples Median Survival in a Pancreatic Cancer ModelPreprint
Hasan, T. G., Saad, M. A., Allen, D., van Bergen, T. D., Morala, J. N., Roberts, H. J., Mai, Z., Chandrasekhara, V., Wang, K. K., Maytin, E. V., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-8912367/v1
High-Throughput Phenotypic Screen to Identify FoxP3 Regulators in Primary T Cells
Wei, Q., Hajjar, E., Cornillot-Clément, S., Solli, E., García‐Díaz, N., Landskron, J., Gade, A., Ahmad, R., & Taskén, K. (2026) · ACS Chemical Biology · doi:10.1021/acschembio.5c01019
Study of the impact of nucleolin targeting on pancreatic ductal adenocarcinoma immune microenvironment
Ponzo, M. (2020) · theses.fr (ABES) · doi:10.70675/05815fd1z5314z4734z8240zd1a40c5a9bdf
Impact du dialogue entre microenvironnement et cellules cancéreuses dans l'adénocarcinome canalaire pancréatique
Nigri, J. (2020) · theses.fr (ABES) · doi:10.70675/8e941da5z4553z4ca3zaf8az9ac2c39c788a
Role of the early stage stroma-immune interactions in the tumor microenvironment of pancreatic adenocarcinoma
Wu, Z. (2021) · theses.fr (ABES) · doi:10.70675/e97fe804z820dz4c4bz843az1f81f0b86c85
Stroma-nerve axis in pancreatic ductal adenocarcinoma: Bidirectional regulatory mechanisms and clinical translation hypothesis
Yu, Y.-N., Jin, S.-Q., Lu, Y.-T., & Han, L.-Z. (2026) · World Journal of Clinical Oncology · doi:10.5306/wjco.v17.i4.117197
Coordinated immune architecture underlies durable survival in pancreatic cancerPreprint
Merali, N., Amin, S., Wu, S., Valverde-Hernandez, C., Gao, W., Chouari, T. A. M., Ragulan, C., Hari, P. S., Bagwan, I., Karanjia, N. D., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.29.721612
Homeobox A10 in gastrointestinal malignancies: unraveling metastatic mechanisms and novel therapeutic opportunities
Kisling, S. G., Shah, A., Johnson, E., Alsafwani, Z. W., Raman, V., & Batra, S. K. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10338-x
Transcriptomic profiling of immune cells in pancreatic cancer
Zhu, X. (2025) · International Conference on Computational Biology and Bioinformatics (ICCBB) · doi:10.1145/3789938.3789976
Metabolic plasticity in the pancreatic cancer metastatic cascade
Zhu, B., Guo, Y., & Lu, Y. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189622 · Cited by 1
CA19-9 induces microenvironment remodeling in pancreatic ductal adenocarcinomaPreprint
Hsu, J., Song, H., Ogawa, S., Kubota, C. S., Peck, K. L., Jacobs, E., Garcia-Rivera, L., Zhu, J., Sui, Y., Jung, W., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.22.727290
Targeting CCR1 Remodels the Tumor Microenvironment and Relieves Immunosuppression in Pancreatic Cancer
Zhang, Y., Kadiyala, P., Yan, W., Brown, K. L., Avritt, F. R., Donahue, K. L., Procario, M. C., Okoye, J. O., Giridharan, T., Elhossiny, A. M., et al. (2026) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-25-1300
Self-citation
Tripartite motif containing 21 autoimmunity primes CD8+ cell–mediated lung inflammation: an in vivo model of interstitial lung disease pathogenesis
Qiu, Y., Wu, Q., Liu, L., Zhao, W., Wang, Y., Wang, F., & Tan, W. (2026) · Arthritis Research & Therapy · doi:10.1186/s13075-026-03850-6
CAF-derived PAI-1 serves as an EGFR ligand and fuels KRAS-mutant pancreatic cancer
Wang, Y., Liu, C., Gao, S., Wang, B., Wang, H., Shi, Z., Xia, S., Li, J., Yao, X., Guo, X., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-75132-3
Risk stratification model based on estimated dose of radiation to immune cells and radiotherapy-related nadir lymphocyte count for predicting the efficacy of consolidation immunotherapy in stage III non-small cell lung cancer
Chen, W., Yu, L., Hou, Q., Cao, X., Zhao, A., Wu, B., Zhou, Y., Zhang, W., Zhao, M., Yao, N. N., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1734341
Treg-derived exosomal miR-146a orchestrates bidirectional Treg-CAF crosstalk to sustain immunosuppressive tumor microenvironments
Ma, H., Zheng, Y., Pei, M., Zeng, Y., Zhang, Z. J., Xu, Y., Wang, X., Zhang, W., Li, N., & Wang, S. (2026) · Medical Oncology · doi:10.1007/s12032-026-03346-y
Interferon-stimulated gene signature predicts clinical response to low-dose IL-2 in immune-mediated inflammatory diseases
Tchitchek, N., Rosenzwajg, M., Lorenzon, R., Rinchai, D., Chaussabel, D., Malek, T. R., & Klatzmann, D. (2026) · Annals of the Rheumatic Diseases · doi:10.1016/j.ard.2026.07.021
Chemotherapy-induced CAF-associated stromal remodeling in a humanized stroma pancreatic ductal adenocarcinoma organoid xenograft model: a comparison between GP and GS
Furihata, K., Iwashita, W., Kurabayashi, A., Furihata, M., Uchida, K., & Taniuchi, K. (2026) · Human Cell · doi:10.1007/s13577-026-01443-8
Cytokine fusion proteins for solid tumor therapy: mechanistic insights and clinical advances
Wang, Y., Zheng, J., Li, Z., Qu, J., Ren, Y., Cai, Z., Li, Y., Sun, W., Jiang, N., Cai, C., et al. (2026) · Journal of Hematology & Oncology · doi:10.1186/s13045-026-01842-2
Spatial Treg niches and the therapeutic reprogramming of tumour tolerance in cancer
Bautista, J., Delgado, M. D. C., Viteri-Recalde, J., Benítez-Núñez, M., Ramírez-Sánchez, D., & López-Cortés, A. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1921036
Mechanism and clinical relevance of metabolic-immune cross-talk in pancreatic tumor microenvironment
Malik, J. A., Jatavath, M., Fishel, M. L., Bhatia, R., & Gautam, S. K. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2026.08.005
Engineering strategies to address immune and delivery barriers in pancreatic ductal adenocarcinoma: a barrier-matched translational framework
Li, Y., Li, Y., Fan, J., San, Z.-Q., & Ye, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1900936
From CAF subtypes to clinically relevant states: cancer-associated fibroblasts in pancreatic ductal adenocarcinoma
Hao, Y., Wang, Y., Du, Q., & Li, G. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1971880
Regulatory T cells in lung adenocarcinoma: Mechanisms of immune escape, prognostic significance and therapeutic opportunities (Review)
Wang, L., & Ruan, C. (2026) · International Journal of Oncology · doi:10.3892/ijo.2026.5943
Serum Cytokine Profiling in Pancreatic Ductal Adenocarcinoma: A Pilot Study of Candidate Discriminators, Sex Differences and Altered Co-Regulation
García-Gómez, J., Agredano-Pérez, S., Rubio-Delgado, D. A., Aguilar‐Lemarroy, A., Jave‐Suárez, L. F., Guevara-Hernández, S. N., Bravo‐Cuéllar, A., Méndez-Clemente, A. S., Hernández‐Flores, G., & Villaseñor-Garcı́a, M. M. (2026) · Biomolecules · doi:10.3390/biom16101492

Authors: Zhang, Y., Lazarus, J., Steele, N. G., Yan, W., Lee, H.-J., Nwosu, Z. C., Halbrook, C. J., Menjivar, R. E., Kemp, S. B., Sirihorachai, V. R., Velez-Delgado, A., Donahue, K., Carpenter, E. S., Brown, K. L., Irizarry-Negron, V., Nevison, A. C., Vinta, A., Anderson, M. A., Crawford, H. C., Lyssiotis, C. A., Frankel, T. L., Bednar, F., & Pasca di Magliano, M.
Affiliations: University of Michigan (US)
1Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Corresponding author: Zhang, Yaqing
Bednar, Filip
ORCID: Zhang, Yaqing
Lazarus, Jenny
Steele, Nina G.
Yan, Wei
Lee, Ho-Joon
Nwosu, Zeribe C.
Halbrook, Christopher J.
Menjivar, Rosa E.
Kemp, Samantha B.
Sirihorachai, Veerin R.
Velez-Delgado, Ashley
Donahue, Katelyn
Carpenter, Eileen S.
Brown, Kristee L.
Irizarry-Negron, Valerie
Anderson, Michelle A.
Crawford, Howard C.
Lyssiotis, Costas A.
Frankel, Timothy L.
Bednar, Filip
Pasca di Magliano, Marina
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2020-03-01
Volume: 10
Issue: 3
Pages: 422-439
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-19-0958
PMC: PMC7224338
OpenAlex: W3000274143
Cited by: 385
References: 73
Citations by year: 2026: 34 · 2025: 49 · 2024: 73 · 2023: 62 · 2022: 66 · 2021: 70 · 2020: 30
FWCI: 20.58
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Cancer Discovery (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: HHS | NIH | National Cancer Institute (R01CA151588, R01CA198074, U01CA224145, P30CA046592, R50CA232985, 3-P30-CA-046592-28-S2, K08CA201581, T32-CA009676)
American Cancer Society (Postdoctoral Award)
University of Michigan Medical School (Michigan Postdoctoral Pioneer Program)
HHS | NIH | National Institute of General Medical Sciences (T32-GM007315, T32-GM113900)
Horace H. Rackham School of Graduate Studies, University of Michigan (Rackham Merit Fellowship)
Association of Academic Surgery (Joel Roslyn Award)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: regulatory T cells, Treg depletion, pancreatic cancer, tumor microenvironment, immunosuppression, TGF-beta, cancer-associated fibroblasts, CCR1, myeloid cell recruitment, CD4+ T cells, pancreatic carcinogenesis, tumor progression
MeSH terms: Animals, Disease Models, Animal, Fibroblasts, Humans, Pancreas, Pancreatic Neoplasms, Transforming Growth Factor beta, Chemokines, CC, T-Lymphocytes, Regulatory, Mice, Receptors, CCR1, Chemokine CCL3, Chemokine CCL8, Tumor Microenvironment, Carcinogenesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks