Research ArticleOriginal Article
Open Access

Myeloid cell reprogramming combined with zoledronic acid effectively suppresses bone metastasis

Yuting Luo, Yiran Cai, Zizheng Jiang, Ke Zheng, Shiji Ren, Lixia Yu, Baorui Liu, Tao Shi and Jia Wei
Cancer Biology & Medicine July 2026, 20260168; DOI: https://doi.org/10.20892/j.issn.2095-3941.2026.0168

References

  1. 1.↵
    2. Coleman RE,
    3. Croucher PI,
    4. Padhani AR,
    5. Clézardin P,
    6. Chow E,
    7. Fallon M, et al.
    Bone metastases. Nat Rev Dis Primers 2020; 6: 83.
    OpenUrlPubMed
  2. 2.↵
    2. Siegel RL,
    3. Kratzer TB,
    4. Giaquinto AN,
    5. Sung H,
    6. Jemal A.
    Cancer statistics, 2025. CA Cancer J Clin. 2025; 75: 10–45.
    OpenUrlCrossRefPubMed
  3. 3.↵
    2. Coleman RE.
    Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006; 12: 6243s–49s.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    2. D’Oronzo S,
    3. Coleman R,
    4. Brown J,
    5. Silvestris F.
    Metastatic bone disease: pathogenesis and therapeutic options. J Bone Oncol. 2019; 15: 100205.
  5. 5.↵
    2. Clézardin P,
    3. Coleman R,
    4. Puppo M,
    5. Ottewell P,
    6. Bonnelye E,
    7. Paycha F, et al.
    Bone metastasis: mechanisms, therapies, and biomarkers. Physiol Rev. 2021; 101: 797–855.
    OpenUrlCrossRefPubMed
  6. 6.↵
    2. Mollica V,
    3. Rizzo A,
    4. Rosellini M,
    5. Marchetti A,
    6. Ricci AD,
    7. Cimadamore A, et al.
    Bone targeting agents in patients with metastatic prostate cancer: state of the art. Cancers (Basel). 2021; 13: 546.
    OpenUrlPubMed
  7. 7.↵
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015; 386: 1353–61.
    OpenUrlCrossRefPubMed
  8. 8.
    2. Fizazi K,
    3. Foulon S,
    4. Carles J,
    5. Roubaud G,
    6. McDermott R,
    7. Fléchon A, et al.
    Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022; 399: 1695–707.
    OpenUrlCrossRefPubMed
  9. 9.↵
    2. Fizazi K,
    3. Carducci M,
    4. Smith M,
    5. Damião R,
    6. Brown J,
    7. Karsh L, et al.
    Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011; 377: 813–22.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.
    2. Gnant M,
    3. Pfeiler G,
    4. Steger GG,
    5. Egle D,
    6. Greil R,
    7. Fitzal F, et al.
    Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019; 20: 339–51.
    OpenUrlCrossRefPubMed
  11. 11.
    2. Peters S,
    3. Danson S,
    4. Hasan B,
    5. Dafni U,
    6. Reinmuth N,
    7. Majem M, et al.
    A randomized open-label phase III trial evaluating the addition of denosumab to standard first-line treatment in advanced NSCLC: the European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR trial. J Thorac Oncol. 2020; 15: 1647–56.
    OpenUrlPubMed
  12. 12.↵
    2. von Moos R,
    3. Costa L,
    4. Gonzalez-Suarez E,
    5. Terpos E,
    6. Niepel D,
    7. Body JJ.
    Management of bone health in solid tumours: from bisphosphonates to a monoclonal antibody. Cancer Treat Rev. 2019; 76: 57–67.
    OpenUrlPubMed
  13. 13.↵
    2. Reinstein ZZ,
    3. Pamarthy S,
    4. Sagar V,
    5. Costa R,
    6. Abdulkadir SA,
    7. Giles FJ, et al.
    Overcoming immunosuppression in bone metastases. Crit Rev Oncol Hematol. 2017; 117: 114–27.
    OpenUrlCrossRefPubMed
  14. 14.
    2. Beer TM,
    3. Kwon ED,
    4. Drake CG,
    5. Fizazi K,
    6. Logothetis C,
    7. Gravis G, et al.
    Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J Clin Oncol. 2017; 35: 40–7.
    OpenUrlCrossRefPubMed
  15. 15.↵
    2. Sharma P,
    3. Pachynski RK,
    4. Narayan V,
    5. Fléchon A,
    6. Gravis G,
    7. Galsky MD, et al.
    Nivolumab plus ipilimumab for metastatic castration-resistant prostate cancer: preliminary analysis of patients in the CheckMate 650 trial. Cancer Cell. 2020; 38: 489–99.e3.
    OpenUrlCrossRefPubMed
  16. 16.
    2. Jiao S,
    3. Subudhi SK,
    4. Aparicio A,
    5. Ge Z,
    6. Guan B,
    7. Miura Y, et al.
    Differences in tumor microenvironment dictate T helper lineage polarization and response to immune checkpoint therapy. Cell. 2019; 179: 1177–90.e13.
    OpenUrlCrossRefPubMed
  17. 17.↵
    2. Wang K,
    3. Gu Y,
    4. Liao Y,
    5. Bang S,
    6. Donnelly CR,
    7. Chen O, et al.
    PD-1 blockade inhibits osteoclast formation and murine bone cancer pain. J Clin Invest. 2020; 130: 3603–20.
    OpenUrlPubMed
  18. 18.↵
    2. Jackett KN,
    3. Browne AT,
    4. Aber ER,
    5. Clements M,
    6. Kaplan RN.
    How the bone microenvironment shapes the pre-metastatic niche and metastasis. Nat Cancer. 2024; 5: 1800–14.
    OpenUrlPubMed
  19. 19.↵
    2. Gungabeesoon J,
    3. Gort-Freitas NA,
    4. Kiss M,
    5. Bolli E,
    6. Messemaker M,
    7. Siwicki M, et al.
    A neutrophil response linked to tumor control in immunotherapy. Cell. 2023; 186: 1448–64.e20.
    OpenUrlCrossRefPubMed
  20. 20.↵
    2. Hirschhorn D,
    3. Budhu S,
    4. Kraehenbuehl L,
    5. Gigoux M,
    6. Schröder D,
    7. Chow A, et al.
    T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants. Cell. 2023; 186: 1432–47.e17.
    OpenUrlCrossRefPubMed
  21. 21.↵
    2. Shi T,
    3. Liu W,
    4. Luo Y,
    5. Liang K,
    6. Ren S,
    7. Song X, et al.
    CHI3L3+ immature neutrophils inhibit anti-tumor immunity and impede immune checkpoint blockade therapy in bone metastases. Cancer Cell. 2025; 43: 1937–57.e11.
    OpenUrlPubMed
  22. 22.↵
    2. He Y,
    3. Luo W,
    4. Liu Y,
    5. Wang Y,
    6. Ma C,
    7. Wu Q, et al.
    IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer. J Clin Invest. 2022; 132: e157917.
  23. 23.
    2. Yue Z,
    3. Niu X,
    4. Yuan Z,
    5. Qin Q,
    6. Jiang W,
    7. He L, et al.
    RSPO2 and RANKL signal through LGR4 to regulate osteoclastic premetastatic niche formation and bone metastasis. J Clin Invest. 2022; 132: e144579.
  24. 24.↵
    2. Cheng JN,
    3. Jin Z,
    4. Su C,
    5. Jiang T,
    6. Zheng X,
    7. Guo J, et al.
    Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts. Cancer Cell. 2025; 43: 1093–107.e9.
    OpenUrlCrossRefPubMed
  25. 25.↵
    2. Ma RY,
    3. Zhang H,
    4. Li XF,
    5. Zhang CB,
    6. Selli C,
    7. Tagliavini G, et al.
    Monocyte-derived macrophages promote breast cancer bone metastasis outgrowth. J Exp Med. 2020; 217: e20191820.
  26. 26.↵
    2. Li XF,
    3. Selli C,
    4. Zhou HL,
    5. Cao J,
    6. Wu S,
    7. Ma RY, et al.
    Macrophages promote anti-androgen resistance in prostate cancer bone disease. J Exp Med. 2023; 220: e20221007.
  27. 27.↵
    2. Kimura H,
    3. Fumoto K,
    4. Shojima K,
    5. Nojima S,
    6. Osugi Y,
    7. Tomihara H, et al.
    CKAP4 is a Dickkopf1 receptor and is involved in tumor progression. J Clin Invest. 2016; 126: 2689–705.
    OpenUrlCrossRefPubMed
  28. 28.↵
    2. Li MH,
    3. Dong LW,
    4. Li SX,
    5. Tang GS,
    6. Pan YF,
    7. Zhang J, et al.
    Expression of cytoskeleton-associated protein 4 is related to lymphatic metastasis and indicates prognosis of intrahepatic cholangiocarcinoma patients after surgery resection. Cancer Lett. 2013; 337: 248–53.
    OpenUrlCrossRefPubMed
  29. 29.↵
    2. Nagoya A,
    3. Sada R,
    4. Kimura H,
    5. Yamamoto H,
    6. Morishita K,
    7. Miyoshi E, et al.
    CKAP4 is a potential exosomal biomarker and therapeutic target for lung cancer. Transl Lung Cancer Res. 2023; 12: 408–26.
    OpenUrlPubMed
  30. 30.↵
    2. Liu Z,
    3. Chen M,
    4. Xie LK,
    5. Liu T,
    6. Zou ZW,
    7. Li Y, et al.
    CLCA4 inhibits cell proliferation and invasion of hepatocellular carcinoma by suppressing epithelial-mesenchymal transition via PI3K/AKT signaling. Aging (Albany NY). 2018; 10: 2570–84.
    OpenUrlPubMed
  31. 31.
    2. Osugi Y,
    3. Fumoto K,
    4. Kikuchi A.
    CKAP4 regulates cell migration via the interaction with and recycling of integrin. Mol Cell Biol. 2019; 39: e00073–19.
    OpenUrlPubMed
  32. 32.↵
    2. Li SX,
    3. Tang GS,
    4. Zhou DX,
    5. Pan YF,
    6. Tan YX,
    7. Zhang J, et al.
    Prognostic significance of cytoskeleton-associated membrane protein 4 and its palmitoyl acyltransferase DHHC2 in hepatocellular carcinoma. Cancer. 2014; 120: 1520–31.
    OpenUrlCrossRefPubMed
  33. 33.↵
    2. D’Amico L,
    3. Mahajan S,
    4. Capietto AH,
    5. Yang Z,
    6. Zamani A,
    7. Ricci B, et al.
    Dickkopf-related protein 1 (Dkk1) regulates the accumulation and function of myeloid derived suppressor cells in cancer. J Exp Med. 2016; 213: 827–40.
    OpenUrlAbstract/FREE Full Text
  34. 34.
    2. Haas MS,
    3. Kagey MH,
    4. Heath H,
    5. Schuerpf F,
    6. Rottman JB,
    7. Newman W.
    mDKN-01, a novel anti-DKK1 mAb, enhances innate immune responses in the tumor microenvironment. Mol Cancer Res. 2021; 19: 717–25.
    OpenUrlAbstract/FREE Full Text
  35. 35.↵
    2. Shi T,
    3. Zhang Y,
    4. Wang Y,
    5. Song X,
    6. Wang H,
    7. Zhou X, et al.
    DKK1 promotes tumor immune evasion and impedes anti–PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer. Cancer Immunol Res. 2022; 10: 1506–24.
    OpenUrlPubMed
  36. 36.↵
    2. Chu T,
    3. Teng J,
    4. Jiang L,
    5. Zhong H,
    6. Han B.
    Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation. Biochem Biophys Res Commun. 2014; 443: 962–8.
    OpenUrlPubMed
  37. 37.
    2. Kasoha M,
    3. Bohle RM,
    4. Seibold A,
    5. Gerlinger C,
    6. Juhasz-Böss I,
    7. Solomayer EF.
    Dickkopf-1 (Dkk1) protein expression in breast cancer with special reference to bone metastases. Clin Exp Metastasis. 2018; 35: 763–75.
    OpenUrlPubMed
  38. 38.↵
    2. Yuan S,
    3. Hoggard NK,
    4. Kantake N,
    5. Hildreth BE 3rd.,
    6. Rosol TJ.
    Effects of Dickkopf-1 (DKK-1) on prostate cancer growth and bone metastasis. Cells. 2023; 12: 2695.
    OpenUrl
  39. 39.↵
    2. Cossarizza A,
    3. Chang HD,
    4. Radbruch A,
    5. Abrignani S,
    6. Addo R,
    7. Akdis M, et al.
    Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition). Eur J Immunol. 2021; 51: 2708–3145.
    OpenUrlCrossRefPubMed
  40. 40.↵
    2. He LH,
    3. Liu M,
    4. He Y,
    5. Xiao E,
    6. Zhao L,
    7. Zhang T, et al.
    TRPV1 deletion impaired fracture healing and inhibited osteoclast and osteoblast differentiation. Sci Rep. 2017; 7: 42385.
  41. 41.↵
    2. Kuchimaru T,
    3. Kataoka N,
    4. Nakagawa K,
    5. Isozaki T,
    6. Miyabara H,
    7. Minegishi M, et al.
    A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries. Nat Commun. 2018; 9: 2981.
    OpenUrlCrossRefPubMed
  42. 42.↵
    2. Sun X,
    3. Park MD,
    4. Merad M,
    5. Brown BD.
    Macrophages: targets for next-generation cancer immunotherapy. Cancer Cell. 2026; 44: 498–518.
    OpenUrlPubMed
  43. 43.↵
    2. Baş Y.
    Is the “PD-L1 macrophage score” possible as an immunotherapy target in colon adenocarcinoma? Gastrointest Tumors. 2024; 11: e003.
  44. 44.↵
    2. Zhu C,
    3. Kong Z,
    4. Wang B,
    5. Cheng W,
    6. Wu A,
    7. Meng X.
    ITGB3/CD61: a hub modulator and target in the tumor microenvironment. Am J Transl Res. 2019; 11: 7195–208.
    OpenUrlPubMed
  45. 45.↵
    2. Husheem M,
    3. Nyman JK,
    4. Vaaraniemi J,
    5. Vaananen HK,
    6. Hentunen TA.
    Characterization of circulating human osteoclast progenitors: development of in vitro resorption assay. Calcif Tissue Int. 2005; 76: 222–30.
    OpenUrlCrossRefPubMed
  46. 46.↵
    2. Dinh HQ,
    3. Eggert T,
    4. Meyer MA,
    5. Zhu YP,
    6. Olingy CE,
    7. Llewellyn R, et al.
    Coexpression of CD71 and CD117 identifies an early unipotent neutrophil progenitor population in human bone marrow. Immunity. 2020; 53: 319–34.e6.
    OpenUrlCrossRefPubMed
  47. 47.
    2. Xie X,
    3. Shi Q,
    4. Wu P,
    5. Zhang X,
    6. Kambara H,
    7. Su J, et al.
    Single-cell transcriptome profiling reveals neutrophil heterogeneity in homeostasis and infection. Nat Immunol. 2020; 21: 1119–33.
    OpenUrlCrossRefPubMed
  48. 48.↵
    2. Liu W,
    3. Shi T,
    4. Lu C,
    5. Che K,
    6. Zhang Z,
    7. Luo Y, et al.
    Human myelocyte and metamyelocyte-stage neutrophils suppress tumor immunity and promote cancer progression. Cell Res. 2025; 35: 588–606.
    OpenUrlPubMed
  49. 49.
    2. Gong Z,
    3. Li Q,
    4. Shi J,
    5. Li P,
    6. Hua L,
    7. Shultz LD, et al.
    Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis. Sci Immunol. 2023; 8: eadd5204.
  50. 50.
    2. Evrard M,
    3. Kwok IWH,
    4. Chong SZ,
    5. Teng KWW,
    6. Becht E,
    7. Chen J, et al.
    Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions. Immunity. 2018; 48: 364–79.e8.
    OpenUrlCrossRefPubMed
  51. 51.
    2. Sagiv JY,
    3. Michaeli J,
    4. Assi S,
    5. Mishalian I,
    6. Kisos H,
    7. Levy L, et al.
    Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell Rep. 2015; 10: 562–73.
    OpenUrlCrossRefPubMed
  52. 52.↵
    2. Rice CM,
    3. Davies LC,
    4. Subleski JJ,
    5. Maio N,
    6. Gonzalez-Cotto M,
    7. Andrews C, et al.
    Tumour-elicited neutrophils engage mitochondrial metabolism to circumvent nutrient limitations and maintain immune suppression. Nat Commun. 2018; 9: 5099.
    OpenUrlCrossRefPubMed
  53. 53.↵
    2. Delobel P,
    3. Ginter B,
    4. Rubio E,
    5. Balabanian K,
    6. Lazennec G.
    CXCR2 intrinsically drives the maturation and function of neutrophils in mice. Front Immunol. 2022; 13: 1005551.
  54. 54.↵
    2. Qian J,
    3. Ma C,
    4. Waterbury QT,
    5. Zhi X,
    6. Moon CS,
    7. Tu R, et al.
    A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis. Cancer Cell. 2025; 43: 1512–29.e11.
    OpenUrlCrossRefPubMed
  55. 55.↵
    2. Mundy GR.
    Mechanisms of bone metastasis. Cancer. 1997; 80: 1546–56.
    OpenUrlCrossRefPubMedWeb of Science
  56. 56.
    2. Guise TA,
    3. Kozlow WM,
    4. Heras-Herzig A,
    5. Padalecki SS,
    6. Yin JJ,
    7. Chirgwin JM.
    Molecular mechanisms of breast cancer metastases to bone. Clin Breast Cancer. 2005; 5: S46–53.
    OpenUrlCrossRefPubMed
  57. 57.↵
    2. Fornetti J,
    3. Welm AL,
    4. Stewart SA.
    Understanding the bone in cancer metastasis. J Bone Miner Res. 2018; 33: 2099–113.
    OpenUrlCrossRefPubMed
  58. 58.↵
    2. Nakashima T,
    3. Hayashi M,
    4. Fukunaga T,
    5. Kurata K,
    6. Oh-Hora M,
    7. Feng JQ, et al.
    Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med. 2011; 17: 1231–34.
    OpenUrlCrossRefPubMed
  59. 59.↵
    2. Waning DL,
    3. Mohammad KS,
    4. Reiken S,
    5. Xie W,
    6. Andersson DC,
    7. John S, et al.
    Excess TGF-β mediates muscle weakness associated with bone metastases in mice. Nat Med. 2015; 21: 1262–71.
    OpenUrlCrossRefPubMed
  60. 60.↵
    2. Kagey MH,
    3. He X.
    Rationale for targeting the Wnt signalling modulator Dickkopf-1 for oncology. Br J Pharmacol. 2017; 174: 4637–50.
    OpenUrlCrossRefPubMed
  61. 61.↵
    2. Goldstein SD,
    3. Trucco M,
    4. Bautista Guzman W,
    5. Hayashi M,
    6. Loeb DM.
    A monoclonal antibody against the Wnt signaling inhibitor dickkopf-1 inhibits osteosarcoma metastasis in a preclinical model. Oncotarget. 2016; 7: 21114–23.
    OpenUrlCrossRefPubMed
  62. 62.↵
    2. Sui Q,
    3. Liu D,
    4. Jiang W,
    5. Tang J,
    6. Kong L,
    7. Han K, et al.
    Dickkopf 1 impairs the tumor response to PD-1 blockade by inactivating CD8+ T cells in deficient mismatch repair colorectal cancer. J Immunother Cancer. 2021; 9: e001498.
  63. 63.↵
    2. Zhuang X,
    3. Zhang H,
    4. Li X,
    5. Li X,
    6. Cong M,
    7. Peng F, et al.
    Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1. Nat Cell Biol. 2017; 19: 1274–85.
    OpenUrlCrossRefPubMed
  64. 64.↵
    2. Ke HZ,
    3. Richards WG,
    4. Li X,
    5. Ominsky MS.
    Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012; 33: 747–83.
    OpenUrlCrossRefPubMedWeb of Science
  65. 65.↵
    2. Takahashi N,
    3. Umezawa R,
    4. Yamamoto T,
    5. Takeda K,
    6. Suzuki Y,
    7. Kishida K, et al.
    A retrospective study of clinical outcomes for patients with esophageal cancer who were treated with radiotherapy alone. Gastrointest Tumors. 2024; 10: 57–66.
    OpenUrlPubMed
  66. 66.↵
    2. Xu J,
    3. Yan D,
    4. Hu R,
    5. Zhang S,
    6. Jiang X.
    Surgical decisions and quality of life after gastrectomy for gastric cancer: update from Asian studies. Gastrointest Tumors. 2024; 11: e002.
  67. 67.↵
    2. Monteran L,
    3. Ershaid N,
    4. Scharff Y,
    5. Zoabi Y,
    6. Sanalla T,
    7. Ding Y, et al.
    Combining TIGIT blockade with MDSC inhibition hinders breast cancer bone metastasis by activating antitumor immunity. Cancer Discov. 2024; 14: 1252–75.
    OpenUrlCrossRefPubMed
  68. 68.↵
    2. Barrett-Lee P,
    3. Casbard A,
    4. Abraham J,
    5. Hood K,
    6. Coleman R,
    7. Simmonds P, et al.
    Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial. Lancet Oncol. 2014; 15: 114–22.
    OpenUrlCrossRefPubMedWeb of Science
  69. 69.
    2. Smith MR,
    3. Halabi S,
    4. Ryan CJ,
    5. Hussain A,
    6. Vogelzang N,
    7. Stadler W, et al.
    Randomized controlled trial of early zoledronic acid in men with castration-sensitive prostate cancer and bone metastases: results of CALGB 90202 (alliance). J Clin Oncol. 2014; 32: 1143–50.
    OpenUrlAbstract/FREE Full Text
  70. 70.↵
    2. Henry DH,
    3. Costa L,
    4. Goldwasser F,
    5. Hirsh V,
    6. Hungria V,
    7. Prausova J, et al.
    Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011; 29: 1125–32.
    OpenUrlAbstract/FREE Full Text
  71. 71.↵
    2. Weber M,
    3. Homm A,
    4. Muller S,
    5. Frey S,
    6. Amann K,
    7. Ries J, et al.
    Zoledronate causes a systemic shift of macrophage polarization towards M1 in vivo. Int J Mol Sci. 2021; 22: 1323.
    OpenUrlPubMed
  72. 72.↵
    2. Klempner SJ,
    3. Sonbol MB,
    4. Wainberg ZA,
    5. Uronis HE,
    6. Chiu VK,
    7. Scott AJ, et al.
    DKN-01 in combination with tislelizumab and chemotherapy as first-line therapy in advanced gastric or gastroesophageal junction adenocarcinoma: DisTinGuish. J Clin Oncol. 2025; 43: 339–49.
    OpenUrlCrossRefPubMed
  73. 73.↵
    2. Shi T,
    3. Wei J.
    Targeting DKK1 to remodel the tumor microenvironment and enhance immune checkpoint blockade therapy. J Clin Oncol. 2025; 43: 350–3.
    OpenUrlPubMed
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