Skip to main content
SpringerLink
Log in

Systemic administration of STING agonist promotes myeloid cells maturation and antitumor immunity through regulating hematopoietic stem and progenitor cell fate

  • Research
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

STING is a pivotal mediator of effective innate and adaptive anti-tumor immunity; however, intratumoral administration of STING agonists have shown limited therapeutic benefit in clinical trials. The systemic effect of the intravenous delivery of STING agonists in cancer is not well-defined. Here, we demonstrated that systemic administration of STING agonist inhibited melanoma growth, improved inflammatory effector cell infiltration, and induced bone marrow mobilization and extramedullary hematopoiesis, causing widespread changes in immune components in the peripheral blood. The systemically administered STING agonist promoted HSC expansion and influenced lineage fate commitment, which was manifested as the differentiation of HSPCs was skewed toward myeloid cells at the expense of B-cell lymphopoiesis and erythropoiesis. Transcriptome analysis revealed upregulation of myeloid lineage differentiation-related and type I interferon-related genes. This myeloid-biased differentiation promoted the production and maturation of myeloid cells toward an activated phenotype. Furthermore, depletion of Gr-1+ myeloid cells attenuated the anti-tumor immunity of STING agonist. Our findings reveal the anti-tumor mechanism of systemic administration of STING agonist that involves modulating HSPC differentiation and promoting myeloid cells maturation. Our study may help explain the limited clinical activity of STING agonists administered intratumorally.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

The Smart-seq2 transcriptome data were deposited in the Gene Expression Omnibus database (accession number GSE192927). All data generated or analyzed in this study were included in this article or in the supplementary information files.

References

  1. Wang RF, Wang HY (2017) Immune targets and neoantigens for cancer immunotherapy and precision medicine. Cell Res 27:11–37. https://doi.org/10.1038/cr.2016.155

    Article  CAS  PubMed  Google Scholar 

  2. Berraondo P, Minute L, Ajona D, Corrales L, Melero I, Pio R (2016) Innate immune mediators in cancer: between defense and resistance. Immunol Rev 274:290–306. https://doi.org/10.1111/imr.12464

    Article  CAS  PubMed  Google Scholar 

  3. Sayour EJ, Mitchell DA (2017) Manipulation of innate and adaptive immunity through cancer vaccines. J Immunol Res 2017:3145742. https://doi.org/10.1155/2017/3145742

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ribas A, Medina T, Kummar S et al (2018) SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase Ib. Multicenter Study Cancer Discov 8:1250–1257. https://doi.org/10.1158/2159-8290.CD-18-0280

    Article  CAS  PubMed  Google Scholar 

  5. Such L, Zhao F, Liu D et al (2020) Targeting the innate immunoreceptor RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy. J Clin Invest 130:4266–4281. https://doi.org/10.1172/JCI131572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ishikawa H, Barber GN (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455:674-U74. https://doi.org/10.1038/nature07317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li A, Yi M, Qin S, Song Y, Chu Q, Wu K (2019) Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy. J Hematol Oncol 12:35. https://doi.org/10.1186/s13045-019-0721-x

    Article  PubMed  PubMed Central  Google Scholar 

  8. Corrales L, Glickman LH, McWhirter SM et al (2015) Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep 11:1018–30. https://doi.org/10.1016/j.celrep.2015.04.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Burdette DL, Vance RE (2013) STING and the innate immune response to nucleic acids in the cytosol. Nat Immunol 14:19–26. https://doi.org/10.1038/ni.2491

    Article  CAS  PubMed  Google Scholar 

  10. Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, Hayakawa Y, Vance RE (2011) STING is a direct innate immune sensor of cyclic di-GMP. Nature 478:515-U111. https://doi.org/10.1038/nature10429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dahal LN, Dou L, Hussain K et al (2017) STING activation reverses lymphoma-mediated resistance to antibody immunotherapy. Can Res 77:3619–31. https://doi.org/10.1158/0008-5472.CAN-16-2784

    Article  CAS  Google Scholar 

  12. Miao L, Qi J, Zhao Q et al (2020) Targeting the STING pathway in tumor-associated macrophages regulates innate immune sensing of gastric cancer cells. Theranostics 10:498–515. https://doi.org/10.7150/thno.37745

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Moore E, Clavijo PE, Davis R, Cash H, Van Waes C, Kim Y, Allen C (2016) Established T cell-inflamed tumors rejected after adaptive resistance was reversed by combination STING activation and PD-1 pathway blockade. Cancer Immunol Res 4:1061–71. https://doi.org/10.1158/2326-6066.Cir-16-0104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sivick KE, Desbien AL, Glickman LH et al (2018) Magnitude of therapeutic STING activation determines CD8(+) T cell-mediated anti-tumor immunity. Cell Rep 25:3074–85 e5. https://doi.org/10.1016/j.celrep.2018.11.047

    Article  CAS  PubMed  Google Scholar 

  15. Jing W, McAllister D, Vonderhaar EP, Palen K, Riese MJ, Gershan J, Johnson BD, Dwinell MB (2019) STING agonist inflames the pancreatic cancer immune microenvironment and reduces tumor burden in mouse models. J Immunother Cancer 7:115. https://doi.org/10.1186/s40425-019-0573-5

    Article  PubMed  PubMed Central  Google Scholar 

  16. Shae D, Becker KW, Christov P et al (2019) Endosomolytic polymersomes increase the activity of cyclic dinucleotide STING agonists to enhance cancer immunotherapy. Nat Nanotechnol 14:269–78. https://doi.org/10.1038/s41565-018-0342-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nicolai CJ, Wolf N, Chang IC, Kirn G, Marcus A, Ndubaku CO, McWhirter SM, Raulet DH (2020) NK cells mediate clearance of CD8(+) T cell-resistant tumors in response to STING agonists. Sci Immunol. https://doi.org/10.1126/sciimmunol.aaz2738

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hiam-Galvez KJ, Allen BM, Spitzer MH (2021) Systemic immunity in cancer. Nat Rev Cancer 21:345–59. https://doi.org/10.1038/s41568-021-00347-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kamran N, Li Y, Sierra M, Alghamri MS, Kadiyala P, Appelman HD, Edwards M, Lowenstein PR, Castro MG (2018) Melanoma induced immunosuppression is mediated by hematopoietic dysregulation. Oncoimmunology 7:e1408750. https://doi.org/10.1080/2162402X.2017.1408750

    Article  PubMed  Google Scholar 

  20. Sio A, Chehal MK, Tsai K et al (2013) Dysregulated hematopoiesis caused by mammary cancer is associated with epigenetic changes and hox gene expression in hematopoietic cells. Can Res 73:5892–904. https://doi.org/10.1158/0008-5472.CAN-13-0842

    Article  CAS  Google Scholar 

  21. Ubellacker JM, Haider MT, DeCristo MJ, Allocca G, Brown NJ, Silver DP, Holen I, McAllister SS (2017) Zoledronic acid alters hematopoiesis and generates breast tumor-suppressive bone marrow cells. Breast Cancer Res 19:23. https://doi.org/10.1186/s13058-017-0815-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Giles AJ, Chien CD, Reid CM, Fry TJ, Park DM, Kaplan RN, Gilbert MR (2016) The functional interplay between systemic cancer and the hematopoietic stem cell niche. Pharmacol Ther 168:53–60. https://doi.org/10.1016/j.pharmthera.2016.09.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wu WC, Sun HW, Chen HT, Liang J, Yu XJ, Wu C, Wang Z, Zheng L (2014) Circulating hematopoietic stem and progenitor cells are myeloid-biased in cancer patients. Proc Natl Acad Sci USA 111:4221–6. https://doi.org/10.1073/pnas.1320753111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Orkin SH, Zon LI (2008) Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132:631–44. https://doi.org/10.1016/j.cell.2008.01.025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Takizawa H, Boettcher S, Manz MG (2012) Demand-adapted regulation of early hematopoiesis in infection and inflammation. Blood 119:2991–3002. https://doi.org/10.1182/blood-2011-12-380113

    Article  CAS  PubMed  Google Scholar 

  26. Strauss L, Mahmoud MAA, Weaver JD et al (2020) Targeted deletion of PD-1 in myeloid cells induces antitumor immunity. Sci Immunol. https://doi.org/10.1126/sciimmunol.aay1863

    Article  PubMed  PubMed Central  Google Scholar 

  27. Rudd CE (2020) A new perspective in cancer immunotherapy: PD-1 on myeloid cells takes center stage in orchestrating immune checkpoint blockade. Sci Immunol. https://doi.org/10.1126/sciimmunol.aaz8128

    Article  PubMed  Google Scholar 

  28. Allen BM, Hiam KJ, Burnett CE et al (2020) Systemic dysfunction and plasticity of the immune macroenvironment in cancer models. Nat Med 26:1125–34. https://doi.org/10.1038/s41591-020-0892-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liao W, Du C, Wang J (2020) The cGAS-STING pathway in hematopoiesis and its physiopathological significance. Front Immunol 11:573915. https://doi.org/10.3389/fimmu.2020.573915

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kobayashi H, Kobayashi CI, Nakamura-Ishizu A et al (2015) Bacterial c-di-GMP affects hematopoietic stem/progenitors and their niches through STING. Cell Rep 11:71–84. https://doi.org/10.1016/j.celrep.2015.02.066

    Article  CAS  PubMed  Google Scholar 

  31. Ramanjulu JM, Pesiridis GS, Yang J et al (2018) Design of amidobenzimidazole STING receptor agonists with systemic activity. Nature 564:439–43. https://doi.org/10.1038/s41586-018-0705-y

    Article  CAS  PubMed  Google Scholar 

  32. Martens A, Wistuba-Hamprecht K, Geukes Foppen M et al (2016) Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab. Clin Cancer Res 22:2908–18. https://doi.org/10.1158/1078-0432.CCR-15-2412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kiel MJ, Yilmaz OH, Iwashita T, Yilmaz OH, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121:1109–21. https://doi.org/10.1016/j.cell.2005.05.026

    Article  CAS  PubMed  Google Scholar 

  34. Socolovsky M, Nam H, Fleming MD, Haase VH, Brugnara C, Lodish HF (2001) Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts. Blood 98:3261–73. https://doi.org/10.1182/blood.v98.12.3261

    Article  CAS  PubMed  Google Scholar 

  35. Ruotsalainen J, Lopez-Ramos D, Rogava M, Shridhar N, Glodde N, Gaffal E, Holzel M, Bald T, Tuting T (2021) The myeloid cell type I IFN system promotes antitumor immunity over pro-tumoral inflammation in cancer T-cell therapy. Clin Transl Immunol 10:e1276. https://doi.org/10.1002/cti2.1276

    Article  CAS  Google Scholar 

  36. Essers MA, Offner S, Blanco-Bose WE, Waibler Z, Kalinke U, Duchosal MA, Trumpp A (2009) IFNalpha activates dormant haematopoietic stem cells in vivo. Nature 458:904–8. https://doi.org/10.1038/nature07815

    Article  CAS  PubMed  Google Scholar 

  37. Gawish R, Bulat T, Biaggio M et al (2019) Myeloid cells restrict MCMV and drive stress-induced extramedullary hematopoiesis through STAT1. Cell Rep 26:2394–406 e5. https://doi.org/10.1016/j.celrep.2019.02.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Matatall KA, Jeong M, Chen S, Sun D, Chen F, Mo Q, Kimmel M, King KY (2016) Chronic infection depletes hematopoietic stem cells through stress-induced terminal differentiation. Cell Rep 17:2584–95. https://doi.org/10.1016/j.celrep.2016.11.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chen MT, Dong L, Zhang XH et al (2015) ZFP36L1 promotes monocyte/macrophage differentiation by repressing CDK6. Sci Rep 5:16229. https://doi.org/10.1038/srep16229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Stanley ER, Chitu V (2014) CSF-1 receptor signaling in myeloid cells. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a021857

    Article  PubMed  PubMed Central  Google Scholar 

  41. Xu J, Escamilla J, Mok S, David J, Priceman S, West B, Bollag G, McBride W, Wu L (2013) CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Can Res 73:2782–94. https://doi.org/10.1158/0008-5472.CAN-12-3981

    Article  CAS  Google Scholar 

  42. Priceman SJ, Sung JL, Shaposhnik Z et al (2010) Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. Blood 115:1461–71. https://doi.org/10.1182/blood-2009-08-237412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Youn JI, Collazo M, Shalova IN, Biswas SK, Gabrilovich DI (2012) Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol 91:167–81. https://doi.org/10.1189/jlb.0311177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bruger AM, Dorhoi A, Esendagli G et al (2019) How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions. Cancer Immunol Immunother 68:631–44. https://doi.org/10.1007/s00262-018-2170-8

    Article  CAS  PubMed  Google Scholar 

  45. Zheng J, Mo J, Zhu T et al (2020) Comprehensive elaboration of the cGAS-STING signaling axis in cancer development and immunotherapy. Mol Cancer 19:133. https://doi.org/10.1186/s12943-020-01250-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Harrington KJ BJ, Ingham M, Strauss J, Cemerski S, Wang M, Tse A, Khilnani A, Marabelle A, Golan T. (2018) Preliminary results of the first-in-human (FIH) study of MK-1454, an agonist of stimulator of interferon genes (STING), as monotherapy or in combination with pembrolizumab (pembro) in patients with advanced solid tumors or lymphomas. ESMO. https://oncologypro.esmo.org/meeting-resources/esmo-2018-congress/preliminary-results-of-the-first-in-human-fih-study-of-mk-1454-an-agonist-of-stimulator-of-interferon-genes-sting-as-monotherapy-or-in-combin

  47. Meric-Bernstam F, Sweis RF, Hodi FS et al (2022) Phase I dose-escalation trial of MIW815 (ADU-S100), an Intratumoral STING agonist, in patients with advanced/metastatic solid tumors or lymphomas. Clin Cancer Res 28:677–88. https://doi.org/10.1158/1078-0432.CCR-21-1963

    Article  CAS  PubMed  Google Scholar 

  48. Funda Meric-Bernstam SKS, Hamid O, Spreafico A, Kasper S, Dummer R, Shimizu T, Steeghs N, Lewis N, Talluto CC, Dolan S, Bean A, Brown R, Trujillo D, Nair N, Luke NJ (2019) Phase Ib study of MIW815 (ADU-S100) in combination with spartalizumab (PDR001) in patients (pts) with advanced/metastatic solid tumors or lymphomas. J Clin Oncol. https://ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.2507

  49. Marvel D, Gabrilovich DI (2015) Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest 125:3356–64. https://doi.org/10.1172/JCI80005

    Article  PubMed  PubMed Central  Google Scholar 

  50. Herman AC, Monlish DA, Romine MP, Bhatt ST, Zippel S, Schuettpelz LG (2016) Systemic TLR2 agonist exposure regulates hematopoietic stem cells via cell-autonomous and cell-non-autonomous mechanisms. Blood Cancer J 6:e437. https://doi.org/10.1038/bcj.2016.45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Li S, Yao JC, Li JT, Schmidt AP, Link DC (2021) TLR7/8 agonist treatment induces an increase in bone marrow resident dendritic cells and hematopoietic progenitor expansion and mobilization. Exp Hematol 96:35-43 e7. https://doi.org/10.1016/j.exphem.2021.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Weiss JM, Guerin MV, Regnier F et al (2017) The STING agonist DMXAA triggers a cooperation between T lymphocytes and myeloid cells that leads to tumor regression. Oncoimmunology 6:e1346765. https://doi.org/10.1080/2162402X.2017.1346765

    Article  PubMed  PubMed Central  Google Scholar 

  53. De Luca K, Frances-Duvert V, Asensio MJ et al (2009) The TLR1/2 agonist PAM(3)CSK(4) instructs commitment of human hematopoietic stem cells to a myeloid cell fate. Leukemia 23:2063–74. https://doi.org/10.1038/leu.2009.155

    Article  CAS  PubMed  Google Scholar 

  54. Ueda Y, Yang K, Foster SJ, Kondo M, Kelsoe G (2004) Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression. J Exp Med 199:47–58. https://doi.org/10.1084/jem.20031104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yang X, Chen D, Long H, Zhu B (2020) The mechanisms of pathological extramedullary hematopoiesis in diseases. Cell Mol Life Sci 77:2723–38. https://doi.org/10.1007/s00018-020-03450-w

    Article  CAS  PubMed  Google Scholar 

  56. Wu C, Ning H, Liu M et al (2018) Spleen mediates a distinct hematopoietic progenitor response supporting tumor-promoting myelopoiesis. J Clin Invest 128:3425–38. https://doi.org/10.1172/JCI97973

    Article  PubMed  PubMed Central  Google Scholar 

  57. Chasis JA, Mohandas N (2008) Erythroblastic islands: niches for erythropoiesis. Blood 112:470–8. https://doi.org/10.1182/blood-2008-03-077883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ramos P, Casu C, Gardenghi S et al (2013) Macrophages support pathological erythropoiesis in polycythemia vera and beta-thalassemia. Nat Med 19:437–45. https://doi.org/10.1038/nm.3126

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Schneider RK, Schenone M, Ferreira MV et al (2016) Rps14 haploinsufficiency causes a block in erythroid differentiation mediated by S100A8 and S100A9. Nat Med 22:288–97. https://doi.org/10.1038/nm.4047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Ganz T (2019) Anemia of inflammation. N Engl J Med 381:1148–57. https://doi.org/10.1056/NEJMra1804281

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Hui Xu and the Laboratory Animal Facility of Peking University Cancer Hospital and Institute for assistance with constructing the mouse model. We are grateful to Peking University Medical and Health Analysis Center for assistance with cell sorting. We also thank Tao Xu and Beijing Biokorad Biotechnology for assistance with FACS analysis, and Annoroad Gene Technology for assistance with transcriptome sequencing and analysis.

Funding

This work was funded by the National Natural Science Foundation of China to Jie Dai (82073011) and to Lu Si (82272676) and the Beijing Municipal Administration of Hospitals’ Ascent Plan to Jie Dai (QML20231107) and to Lu Si (DFL20220901).

Author information

Author notes

  1. Tianxiao Xu and Jie Dai contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, 52# Fucheng Road, Haidian District, Beijing, 100142, China

    Tianxiao Xu, Jie Dai, Lirui Tang, Linzi Sun, Lu Si & Jun Guo

  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital and Institute, 52# Fucheng Road, Haidian District, Beijing, 100142, China

    Jun Guo

Authors
  1. Tianxiao Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lirui Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Linzi Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lu Si
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jun Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization: TX, JD, LS, JG; data curation: TX, JD, LS, JG; formal analysis: TX, JD, LT, LS, LS, JG; methodology: TX, JD, LT, LS; investigation: TX, JD, LT, LS; supervision: JD, LS, JG; validation: TX, JD, LT, LS; original draft preparation: TX, JD; revision and editing: LT, LS, LS, JG.

Corresponding authors

Correspondence to Lu Si or Jun Guo.

Ethics declarations

Conflict of interest

The authors state no conflict of interest.

Ethical approval

The studies involving mice were reviewed and approved by the Ethics Committee of Peking University Cancer Hospital and Institute.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 26258 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, T., Dai, J., Tang, L. et al. Systemic administration of STING agonist promotes myeloid cells maturation and antitumor immunity through regulating hematopoietic stem and progenitor cell fate. Cancer Immunol Immunother 72, 3491–3505 (2023). https://doi.org/10.1007/s00262-023-03502-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-023-03502-7

Keywords

Search

Navigation