nach oben

Erschienen in:

07.03.2023 | Research

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation

verfasst von: Yun-Shan Lin, Shu-Fen Chiang, Chia-Yi Chen, Wei-Ze Hong, Tsung-Wei Chen, William Tzu-Liang Chen, Tao-Wei Ke, Pei-Chen Yang, Ji-An Liang, An‑Cheng Shiau, K. S. Clifford Chao, Kevin Chih-Yang Huang

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2023

Einloggen, um Zugang zu erhalten

Abstract

The CD39-CD73–adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I–IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084–1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103–1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45⁺ and CD8⁺ immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.

Nur mit Berechtigung zugänglich

Huang CY, Chiang SF, Ke TW, Chen TW, You YS, Chen WT et al (2018) Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II-III colorectal cancer. Sci Rep 8(1):15658. https://doi.org/10.1038/s41598-018-33927-5CrossRefPubMedPubMedCentral

Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72(1):7–33. https://doi.org/10.3322/caac.21708CrossRefPubMed

Adlard JW, Richman SD, Seymour MT, Quirke P (2002) Prediction of the response of colorectal cancer to systemic therapy. Lancet Oncol 3(2):75–82. https://doi.org/10.1016/s1470-2045(02)00648-4CrossRefPubMed

McCleary NJ, Meyerhardt JA, Green E, Yothers G, de Gramont A, Van Cutsem E et al (2013) Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol 31(20):2600–2606. https://doi.org/10.1200/JCO.2013.49.6638CrossRefPubMedPubMedCentral

Huang CY, Chiang SF, Ke TW, Chen TW, Lan YC, You YS et al (2018) Cytosolic high-mobility group box protein 1 (HMGB1) and/or PD-1+ TILs in the tumor microenvironment may be contributing prognostic biomarkers for patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Cancer Immunol Immunother 67(4):551–562. https://doi.org/10.1007/s00262-017-2109-5CrossRefPubMed

Chen TW, Huang KC, Chiang SF, Chen WT, Ke TW, Chao KSC (2019) Prognostic relevance of programmed cell death-ligand 1 expression and CD8+ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy. J Cancer Res Clin Oncol 145(4):1043–1053. https://doi.org/10.1007/s00432-019-02874-7CrossRefPubMed

Wang J, Yuan R, Song W, Sun J, Liu D, Li Z (2017) PD-1, PD-L1 (B7–H1) and Tumor-site immune modulation therapy: the historical perspective. J Hematol Oncol 10(1):34. https://doi.org/10.1186/s13045-017-0403-5CrossRefPubMedPubMedCentral

Xu-Monette ZY, Zhang M, Li J, Young KH (2017) PD-1/PD-L1 blockade: have we found the key to unleash the antitumor immune response? Front Immunol 8:1597. https://doi.org/10.3389/fimmu.2017.01597CrossRefPubMedPubMedCentral

Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C et al (2013) Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci U S A 110(36):14711–14716. https://doi.org/10.1073/pnas.1308209110CrossRefPubMedPubMedCentral

10.

Leclerc BG, Charlebois R, Chouinard G, Allard B, Pommey S, Saad F et al (2016) CD73 expression is an independent prognostic factor in prostate cancer. Clin Cancer Res 22(1):158–166. https://doi.org/10.1158/1078-0432.CCR-15-1181CrossRefPubMed

11.

Hatfield SM, Kjaergaard J, Lukashev D, Schreiber TH, Belikoff B, Abbott R et al (2015) Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aaa1260CrossRefPubMedPubMedCentral

12.

Antonioli L, Pacher P, Vizi ES, Hasko G (2013) CD39 and CD73 in immunity and inflammation. Trends Mol Med 19(6):355–367. https://doi.org/10.1016/j.molmed.2013.03.005CrossRefPubMedPubMedCentral

13.

Synnestvedt K, Furuta GT, Comerford KM, Louis N, Karhausen J, Eltzschig HK et al (2002) Ecto-5’-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest 110(7):993–1002. https://doi.org/10.1172/JCI15337CrossRefPubMedPubMedCentral

14.

Niemela J, Henttinen T, Yegutkin GG, Airas L, Kujari AM, Rajala P et al (2004) IFN-alpha induced adenosine production on the endothelium: a mechanism mediated by CD73 (ecto-5’-nucleotidase) up-regulation. J Immunol 172(3):1646–1653. https://doi.org/10.4049/jimmunol.172.3.1646CrossRefPubMed

15.

Burnstock G, Di Virgilio F (2013) Purinergic signalling and cancer. Purinergic Signal 9(4):491–540. https://doi.org/10.1007/s11302-013-9372-5CrossRefPubMedPubMedCentral

16.

Loi S, Pommey S, Haibe-Kains B, Beavis PA, Darcy PK, Smyth MJ et al (2013) CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proc Natl Acad Sci U S A 110(27):11091–11096. https://doi.org/10.1073/pnas.1222251110CrossRefPubMedPubMedCentral

17.

Zhang B, Song B, Wang X, Chang XS, Pang T, Zhang X et al (2015) The expression and clinical significance of CD73 molecule in human rectal adenocarcinoma. Tumour Biol 36(7):5459–5466. https://doi.org/10.1007/s13277-015-3212-xCrossRefPubMed

18.

Yegutkin GG, Marttila-Ichihara F, Karikoski M, Niemela J, Laurila JP, Elima K et al (2011) Altered purinergic signaling in CD73-deficient mice inhibits tumor progression. Eur J Immunol 41(5):1231–1241. https://doi.org/10.1002/eji.201041292CrossRefPubMed

19.

Perrot I, Michaud HA, Giraudon-Paoli M, Augier S, Docquier A, Gros L et al (2019) Blocking antibodies targeting the CD39/CD73 immunosuppressive pathway unleash immune responses in combination cancer therapies. Cell Rep 27(8):2411–2425. https://doi.org/10.1016/j.celrep.2019.04.091CrossRefPubMed

20.

Huang KC, Chiang SF, Chen TW, Chen WT, Yang PC, Ke TW et al (2020) Prognostic relevance of programmed cell death 1 ligand 2 (PDCD1LG2/PD-L2) in patients with advanced stage colon carcinoma treated with chemotherapy. Sci Rep 10(1):22330. https://doi.org/10.1038/s41598-020-79419-3CrossRefPubMedPubMedCentral

21.

Lin TY, Fan CW, Maa MC, Leu TH (2015) Lipopolysaccharide-promoted proliferation of Caco-2 cells is mediated by c-Src induction and ERK activation. Biomedicine (Taipei) 5(1):5. https://doi.org/10.7603/s40681-015-0005-xCrossRefPubMed

22.

Wang X, Sheu JJ, Lai MT, Yin-Yi Chang C, Sheng X, Wei L et al (2018) RSF-1 overexpression determines cancer progression and drug resistance in cervical cancer. Biomedicine (Taipei) 8(1):4. https://doi.org/10.1051/bmdcn/2018080104CrossRefPubMed

23.

Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A et al (2015) Proteomics tissue-based map of the human proteome. Science 347(6220):1260419. https://doi.org/10.1126/science.1260419CrossRefPubMed

24.

Uhlen M, Zhang C, Lee S, Sjostedt E, Fagerberg L, Bidkhori G et al (2017) A pathology atlas of the human cancer transcriptome. Science. https://doi.org/10.1126/science.aan2507CrossRefPubMed

25.

Hoadley KA, Yau C, Hinoue T, Wolf DM, Lazar AJ, Drill E et al (2018) Cell-of-origin patterns dominate the molecular classification of 10,000 tumors from 33 types of cancer. Cell 173(2):291–304. https://doi.org/10.1016/j.cell.2018.03.022CrossRefPubMedPubMedCentral

26.

Huang KC, Lai CY, Hong WZ, Chang HY, Lin PC, Chiang SF et al (2022) A novel engineered AAV-based neoantigen vaccine in combination with radiotherapy eradicates tumors. Cancer Immunol Res. https://doi.org/10.1158/2326-6066.CIR-22-0318CrossRefPubMedPubMedCentral

27.

Huang KC, Chiang SF, Chang HY, Chen WT, Yang PC, Chen TW et al (2022) Engineered sTRAIL-armed MSCs overcome STING deficiency to enhance the therapeutic efficacy of radiotherapy for immune checkpoint blockade. Cell Death Dis 13(7):610. https://doi.org/10.1038/s41419-022-05069-0CrossRefPubMedPubMedCentral

28.

Chen TW, Hung WZ, Chiang SF, Chen WT, Ke TW, Liang JA et al (2022) Dual inhibition of TGFbeta signaling and CSF1/CSF1R reprograms tumor-infiltrating macrophages and improves response to chemotherapy via suppressing PD-L1. Cancer Lett. https://doi.org/10.1016/j.canlet.2022.215795CrossRefPubMedPubMedCentral

29.

Huang KC, Chiang SF, Yang PC, Ke TW, Chen TW, Hu CH et al (2021) Immunogenic cell death by the novel topoisomerase i inhibitor tlc388 enhances the therapeutic efficacy of radiotherapy. Cancers (Basel). https://doi.org/10.3390/cancers13061218CrossRefPubMedPubMedCentral

30.

Huang KC, Chiang SF, Chen WT, Chen TW, Hu CH, Yang PC et al (2020) Decitabine augments chemotherapy-induced PD-L1 upregulation for PD-L1 blockade in colorectal cancer. Cancers (Basel). https://doi.org/10.3390/cancers12020462CrossRefPubMedPubMedCentral

31.

Wennerberg E, Spada S, Rudqvist NP, Lhuillier C, Gruber S, Chen Q et al (2020) CD73 blockade promotes dendritic cell infiltration of irradiated tumors and tumor rejection. Cancer Immunol Res 8(4):465–478. https://doi.org/10.1158/2326-6066.CIR-19-0449CrossRefPubMedPubMedCentral

32.

Stagg J, Smyth MJ (2010) Extracellular adenosine triphosphate and adenosine in cancer. Oncogene 29(39):5346–5358. https://doi.org/10.1038/onc.2010.292CrossRefPubMed

33.

Messaoudi N, Cousineau I, Arslanian E, Henault D, Stephen D, Vandenbroucke-Menu F et al (2020) Prognostic value of CD73 expression in resected colorectal cancer liver metastasis. Oncoimmunology 9(1):1746138. https://doi.org/10.1080/2162402X.2020.1746138CrossRefPubMedPubMedCentral

34.

Wu XR, He XS, Chen YF, Yuan RX, Zeng Y, Lian L et al (2012) High expression of CD73 as a poor prognostic biomarker in human colorectal cancer. J Surg Oncol 106(2):130–137. https://doi.org/10.1002/jso.23056CrossRefPubMed

35.

Ren ZH, Lin CZ, Cao W, Yang R, Lu W, Liu ZQ et al (2016) CD73 is associated with poor prognosis in HNSCC. Oncotarget 7(38):61690–61702. https://doi.org/10.18632/oncotarget.11435CrossRefPubMedPubMedCentral

36.

Samanta D, Park Y, Ni X, Li H, Zahnow CA, Gabrielson E et al (2018) Chemotherapy induces enrichment of CD47(+)/CD73(+)/PDL1(+) immune evasive triple-negative breast cancer cells. Proc Natl Acad Sci U S A 115(6):E1239–E1248. https://doi.org/10.1073/pnas.1718197115CrossRefPubMedPubMedCentral

37.

Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72. https://doi.org/10.1146/annurev-immunol-032712-100008CrossRefPubMed

38.

Beavis PA, Milenkovski N, Henderson MA, John LB, Allard B, Loi S et al (2015) Adenosine receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced antitumor t-cell responses. Cancer Immunol Res 3(5):506–517. https://doi.org/10.1158/2326-6066.CIR-14-0211CrossRefPubMed

39.

Bhattarai S, Freundlieb M, Pippel J, Meyer A, Abdelrahman A, Fiene A et al (2015) alpha, beta-methylene-ADP (AOPCP) derivatives and analogues: development of potent and selective ecto-5’-nucleotidase (CD73) inhibitors. J Med Chem 58(15):6248–6263. https://doi.org/10.1021/acs.jmedchem.5b00802CrossRefPubMed

40.

Stagg J, Divisekera U, McLaughlin N, Sharkey J, Pommey S, Denoyer D et al (2010) Anti-CD73 antibody therapy inhibits breast tumor growth and metastasis. Proc Natl Acad Sci U S A 107(4):1547–1552. https://doi.org/10.1073/pnas.0908801107CrossRefPubMedPubMedCentral

41.

Allard B, Pommey S, Smyth MJ, Stagg J (2013) Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res 19(20):5626–5635. https://doi.org/10.1158/1078-0432.CCR-13-0545CrossRefPubMed

42.

Hay CM, Sult E, Huang Q, Mulgrew K, Fuhrmann SR, McGlinchey KA et al (2016) Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology 5(8):e1208875. https://doi.org/10.1080/2162402X.2016.1208875CrossRefPubMedPubMedCentral

43.

Vogt TJ, Gevensleben H, Dietrich J, Kristiansen G, Bootz F, Landsberg J et al (2018) Detailed analysis of adenosine A2a receptor (ADORA2A) and CD73 (5’-nucleotidase, ecto, NT5E) methylation and gene expression in head and neck squamous cell carcinoma patients. Oncoimmunology 7(8):e1452579. https://doi.org/10.1080/2162402X.2018.1452579CrossRefPubMedPubMedCentral

44.

Chen Q, Pu N, Yin H, Zhang J, Zhao G, Lou W et al (2020) CD73 acts as a prognostic biomarker and promotes progression and immune escape in pancreatic cancer. J Cell Mol Med 24(15):8674–8686. https://doi.org/10.1111/jcmm.15500CrossRefPubMedPubMedCentral

45.

Huang KC, Chiang SC, Ke TW, Chen TW, Hu CH, Yang PC et al (2021) DNMT1 constrains IFNβ-mediated anti-tumor immunity and PD-L1 expression to reduce the efficacy of radiotherapy and immunotherapy. OncoImmunology 10(1):1989790. https://doi.org/10.1080/2162402X.2021.1989790CrossRef

46.

Wang YJ, Fletcher R, Yu J, Zhang L (2018) Immunogenic effects of chemotherapy-induced tumor cell death. Genes Dis 5(3):194–203. https://doi.org/10.1016/j.gendis.2018.05.003CrossRefPubMedPubMedCentral

47.

Young CNJ, Gorecki DC (2018) P2RX7 purinoceptor as a therapeutic target-the second coming? Front Chem 6:248. https://doi.org/10.3389/fchem.2018.00248CrossRefPubMedPubMedCentral

48.

Tsukui H, Horie H, Koinuma K, Ohzawa H, Sakuma Y, Hosoya Y et al (2020) CD73 blockade enhances the local and abscopal effects of radiotherapy in a murine rectal cancer model. BMC Cancer 20(1):411. https://doi.org/10.1186/s12885-020-06893-3CrossRefPubMedPubMedCentral

49.

Zhang B, Cheng B, Li FS, Ding JH, Feng YY, Zhuo GZ et al (2015) High expression of CD39/ENTPD1 in malignant epithelial cells of human rectal adenocarcinoma. Tumour Biol 36(12):9411–9419. https://doi.org/10.1007/s13277-015-3683-9CrossRefPubMed

Titel: Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation
verfasst von: Yun-Shan Lin
Shu-Fen Chiang
Chia-Yi Chen
Wei-Ze Hong
Tsung-Wei Chen
William Tzu-Liang Chen
Tao-Wei Ke
Pei-Chen Yang
Ji-An Liang
An‑Cheng Shiau
K. S. Clifford Chao
Kevin Chih-Yang Huang
Publikationsdatum: 07.03.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 7/2023
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-023-03416-4

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation

Abstract

Neu im Fachgebiet Onkologie

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Erhöhte Mortalität bei postpartalem Brustkrebs

Update Onkologie

Klimawandel und Gesundheit: Was Sie in der Hausarztpraxis wissen müssen und tun können

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2023

Preliminary clinical study of personalized neoantigen vaccine therapy for microsatellite stability (MSS)-advanced colorectal cancer

Clinicopathological significance of peritumoral alveolar macrophages in patients with resected early-stage lung squamous cell carcinoma

Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy

Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study

Immune checkpoint inhibition combined with targeted therapy using a novel virus-like drug conjugate induces complete responses in a murine model of local and distant tumors

CiTSA: a comprehensive platform provides experimentally supported signatures of cancer immunotherapy and analysis tools based on bulk and scRNA-seq data

Neu im Fachgebiet Onkologie

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Alter verschlechtert Prognose bei Endometriumkarzinom

Darf man die Behandlung eines Neonazis ablehnen?

Erhöhte Mortalität bei postpartalem Brustkrebs

Update Onkologie