The CD47/TSP-1 axis: a promising avenue for ovarian cancer treatment and biomarker research.
CD47
Neoadjuvant chemotherapy
Ovarian cancer
PARP
TSP-1
Journal
Molecular cancer
ISSN: 1476-4598
Titre abrégé: Mol Cancer
Pays: England
ID NLM: 101147698
Informations de publication
Date de publication:
14 Aug 2024
14 Aug 2024
Historique:
received:
13
05
2024
accepted:
25
07
2024
medline:
14
8
2024
pubmed:
14
8
2024
entrez:
13
8
2024
Statut:
epublish
Résumé
Ovarian cancer (OC) remains one of the most challenging and deadly malignancies facing women today. While PARP inhibitors (PARPis) have transformed the treatment landscape for women with advanced OC, many patients will relapse and the PARPi-resistant setting is an area of unmet medical need. Traditional immunotherapies targeting PD-1/PD-L1 have failed to show any benefit in OC. The CD47/TSP-1 axis may be relevant in OC. We aimed to describe changes in CD47 expression with platinum therapy and their relationship with immune features and prognosis. Tumor and blood samples collected from OC patients in the CHIVA trial were assessed for CD47 and TSP-1 before and after neoadjuvant chemotherapy (NACT) and multiplex analysis was used to investigate immune markers. Considering the therapeutic relevance of targeting the CD47/TSP-1 axis, we used the CD47-derived TAX2 peptide to selectively antagonize it in a preclinical model of aggressive ovarian carcinoma. Significant reductions in CD47 expression were observed post NACT. Tumor patients having the highest CD47 expression profile at baseline showed the greatest CD4 Our study thus (1) proposes a CD47-based stratification of patients who may be most likely to benefit from postoperative immunotherapy, and (2) suggests that TAX2 is a potential alternative therapy for patients relapsing on PARP inhibitors.
Sections du résumé
BACKGROUND
BACKGROUND
Ovarian cancer (OC) remains one of the most challenging and deadly malignancies facing women today. While PARP inhibitors (PARPis) have transformed the treatment landscape for women with advanced OC, many patients will relapse and the PARPi-resistant setting is an area of unmet medical need. Traditional immunotherapies targeting PD-1/PD-L1 have failed to show any benefit in OC. The CD47/TSP-1 axis may be relevant in OC. We aimed to describe changes in CD47 expression with platinum therapy and their relationship with immune features and prognosis.
METHODS
METHODS
Tumor and blood samples collected from OC patients in the CHIVA trial were assessed for CD47 and TSP-1 before and after neoadjuvant chemotherapy (NACT) and multiplex analysis was used to investigate immune markers. Considering the therapeutic relevance of targeting the CD47/TSP-1 axis, we used the CD47-derived TAX2 peptide to selectively antagonize it in a preclinical model of aggressive ovarian carcinoma.
RESULTS
RESULTS
Significant reductions in CD47 expression were observed post NACT. Tumor patients having the highest CD47 expression profile at baseline showed the greatest CD4
CONCLUSIONS
CONCLUSIONS
Our study thus (1) proposes a CD47-based stratification of patients who may be most likely to benefit from postoperative immunotherapy, and (2) suggests that TAX2 is a potential alternative therapy for patients relapsing on PARP inhibitors.
Identifiants
pubmed: 39138571
doi: 10.1186/s12943-024-02073-0
pii: 10.1186/s12943-024-02073-0
doi:
Substances chimiques
CD47 Antigen
0
Biomarkers, Tumor
0
CD47 protein, human
0
Thrombospondin 1
0
thrombospondin-1, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
166Informations de copyright
© 2024. The Author(s).
Références
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clinicians. 2021;71:209–49.
doi: 10.3322/caac.21660
Crosby D, Bhatia S, Brindle KM, Coussens LM, Dive C, Emberton M, et al. Early detection of cancer. Science. 2022;375:eaay9040.
pubmed: 35298272
doi: 10.1126/science.aay9040
Perez-Fidalgo JA, Grau F, Fariñas L, Oaknin A. Systemic treatment of newly diagnosed advanced epithelial ovarian cancer: From chemotherapy to precision medicine. Crit Rev Oncol Hematol. 2021;158: 103209.
pubmed: 33388455
doi: 10.1016/j.critrevonc.2020.103209
Lheureux S, Braunstein M, Oza AM. Epithelial ovarian cancer: Evolution of management in the era of precision medicine. CA Cancer J Clin. 2019;69:280–304.
pubmed: 31099893
doi: 10.3322/caac.21559
Vergote I, Gonzalez-Martin A, Lorusso D, Gourley C, Mirza MR, Kurtz J-E, et al. Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup. Lancet Oncol. 2022;23:e374–84.
pubmed: 35901833
pmcid: 9465953
doi: 10.1016/S1470-2045(22)00139-5
Tew WP, Lacchetti C, Kohn EC, PARP Inhibitors in the Management of Ovarian Cancer Guideline Expert Panel. Poly(ADP-Ribose) Polymerase Inhibitors in the Management of Ovarian Cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2022;40:3878–81.
pubmed: 36150092
doi: 10.1200/JCO.22.01934
Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. The Lancet. 2010;376:245–51.
doi: 10.1016/S0140-6736(10)60893-8
Chardin L, Leary A. Immunotherapy in Ovarian Cancer: Thinking Beyond PD-1/PD-L1. Front Oncol. 2021;11: 795547.
pubmed: 34966689
pmcid: 8710491
doi: 10.3389/fonc.2021.795547
Moore KN, Bookman M, Sehouli J, Miller A, Anderson C, Scambia G, et al. Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol. 2021;39:1842–55.
pubmed: 33891472
pmcid: 8189598
doi: 10.1200/JCO.21.00306
Kurtz J-E, Pujade-Lauraine E, Oaknin A, Belin L, Leitner K, Cibula D, et al. Atezolizumab Combined With Bevacizumab and Platinum-Based Therapy for Platinum-Sensitive Ovarian Cancer: Placebo-Controlled Randomized Phase III ATALANTE/ENGOT-ov29 Trial. J Clin Oncol. 2023;41:4768–78.
pubmed: 37643382
pmcid: 10602539
doi: 10.1200/JCO.23.00529
Blanc-Durand F, Pautier P, Michels J, Leary A. Targeting the immune microenvironment in ovarian cancer therapy-mission impossible? ESMO Open. 2024;9: 102936.
pubmed: 38492450
pmcid: 10955311
doi: 10.1016/j.esmoop.2024.102936
Elisa Yaniz-Galende, Qinghe Zeng, Juan Francisco Bejar-Grau, Christophe Klein, Felix Blanc-Durand, Audrey Le Formal, Eric Pujade-Lauraine, Laure Chardin, Elodie Edmond, Virginie Marty, Isabelle Ray-Coquard, Florence Joly, Gwenael Ferron, Patricia Pautier, Dominique Berton-Rigaud, Alain Lortholary, Nadine Dohollou, Christophe Desauw, Michel Fabbro, Emmanuelle Malaurie, Nathalie Bonichon-Lamaichhane, Diana Bello Roufai, Justine Gantzer, Etienne Rouleau, Catherine Genestie, Alexandra Leary. Spatial multiplexed immune profiling of EOC and evolution under NACT. CCR.
Ray-Coquard I, Leary A, Pignata S, Cropet C, González-Martín A, Marth C, et al. Olaparib plus bevacizumab first-line maintenance in ovarian cancer: final overall survival results from the PAOLA-1/ENGOT-ov25 trial. Ann Oncol. 2023;34:681–92.
pubmed: 37211045
doi: 10.1016/j.annonc.2023.05.005
O’Malley DM, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, et al. Clinical and molecular characteristics of ARIEL3 patients who derived exceptional benefit from rucaparib maintenance treatment for high-grade ovarian carcinoma. Gynecol Oncol. 2022;167:404–13.
pubmed: 36273926
pmcid: 10339359
doi: 10.1016/j.ygyno.2022.08.021
DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim B-G, Oaknin A, et al. Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial. J Clin Oncol. 2023;41:609–17.
pubmed: 36082969
doi: 10.1200/JCO.22.01549
Wang L, Wang X, Zhu X, Zhong L, Jiang Q, Wang Y, et al. Drug resistance in ovarian cancer: from mechanism to clinical trial. Mol Cancer. 2024;23:66.
pubmed: 38539161
pmcid: 10976737
doi: 10.1186/s12943-024-01967-3
Li H, Liu Z-Y, Wu N, Chen Y-C, Cheng Q, Wang J. PARP inhibitor resistance: the underlying mechanisms and clinical implications. Mol Cancer. 2020;19:107.
pubmed: 32563252
pmcid: 7305609
doi: 10.1186/s12943-020-01227-0
Son J, Hsieh RC-E, Lin HY, Krause KJ, Yuan Y, Biter AB, et al. Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data. Front Immunol. 2022;13:1027235.
pubmed: 36439116
pmcid: 9691650
doi: 10.3389/fimmu.2022.1027235
Denèfle T, Boullet H, Herbi L, Newton C, Martinez-Torres A-C, Guez A, et al. Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies. J Med Chem. 2016;59:8412–21.
pubmed: 27526615
doi: 10.1021/acs.jmedchem.6b00781
Kaur S, Roberts DD. Divergent modulation of normal and neoplastic stem cells by thrombospondin-1 and CD47 signaling. Int J Biochem Cell Biol. 2016;81:184–94.
pubmed: 27163531
pmcid: 5097897
doi: 10.1016/j.biocel.2016.05.005
Maxhimer JB, Soto-Pantoja DR, Ridnour LA, Shih HB, Degraff WG, Tsokos M, et al. Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci Transl Med. 2009;1:3ra7.
pubmed: 20161613
pmcid: 2811586
doi: 10.1126/scitranslmed.3000139
Stirling ER, Terabe M, Wilson AS, Kooshki M, Yamaleyeva LM, Alexander-Miller MA, et al. Targeting the CD47/thrombospondin-1 signaling axis regulates immune cell bioenergetics in the tumor microenvironment to potentiate antitumor immune response. J Immunother Cancer. 2022;10: e004712.
pubmed: 36418073
pmcid: 9685258
doi: 10.1136/jitc-2022-004712
Jeanne A, Sarazin T, Charlé M, Moali C, Fichel C, Boulagnon-Rombi C, et al. Targeting Ovarian Carcinoma with TSP-1:CD47 Antagonist TAX2 Activates Anti-Tumor Immunity. Cancers (Basel). 2021;13:5019.
pubmed: 34638503
doi: 10.3390/cancers13195019
Xiao Q, Li X, Liu C, Jiang Y, He Y, Zhang W, et al. Improving cancer immunotherapy via co-delivering checkpoint blockade and thrombospondin-1 downregulator. Acta Pharm Sin B. 2023;13:3503–17.
pubmed: 37655330
doi: 10.1016/j.apsb.2022.07.012
Miller TW, Kaur S, Ivins-O’Keefe K, Roberts DD. Thrombospondin-1 is a CD47-dependent endogenous inhibitor of hydrogen sulfide signaling in T cell activation. Matrix Biol. 2013;32:316–24.
pubmed: 23499828
pmcid: 3706541
doi: 10.1016/j.matbio.2013.02.009
Stein EV, Miller TW, Ivins-O’Keefe K, Kaur S, Roberts DD. Secreted Thrombospondin-1 Regulates Macrophage Interleukin-1β Production and Activation through CD47. Sci Rep. 2016;6:19684.
pubmed: 26813769
pmcid: 4728557
doi: 10.1038/srep19684
Isenberg JS, Montero E. Tolerating CD47. Clin Transl Med. 2024;14: e1584.
pubmed: 38362603
pmcid: 10870051
doi: 10.1002/ctm2.1584
Jeanne A, Sick E, Devy J, Floquet N, Belloy N, Theret L, et al. Identification of TAX2 peptide as a new unpredicted anti-cancer agent. Oncotarget. 2015;6:17981–8000.
pubmed: 26046793
pmcid: 4627230
doi: 10.18632/oncotarget.4025
Jeanne A, Boulagnon-Rombi C, Devy J, Théret L, Fichel C, Bouland N, et al. Matricellular TSP-1 as a target of interest for impeding melanoma spreading: towards a therapeutic use for TAX2 peptide. Clin Exp Metastasis. 2016;33:637–49.
pubmed: 27349907
doi: 10.1007/s10585-016-9803-0
Jeanne A, Martiny L, Dedieu S. Thrombospondin-targeting TAX2 peptide impairs tumor growth in preclinical mouse models of childhood neuroblastoma. Pediatr Res. 2017;81:480–8.
pubmed: 27842053
doi: 10.1038/pr.2016.242
Daubon T, Léon C, Clarke K, Andrique L, Salabert L, Darbo E, et al. Deciphering the complex role of thrombospondin-1 in glioblastoma development. Nat Commun. 2019;10:1146.
pubmed: 30850588
pmcid: 6408502
doi: 10.1038/s41467-019-08480-y
Jeanne A, Untereiner V, Perreau C, Proult I, Gobinet C, Boulagnon-Rombi C, et al. Lumican delays melanoma growth in mice and drives tumor molecular assembly as well as response to matrix-targeted TAX2 therapeutic peptide. Sci Rep. 2017;7:7700.
pubmed: 28794454
pmcid: 5550434
doi: 10.1038/s41598-017-07043-9
Ferron G, De Rauglaudre G, Becourt S, Delanoy N, Joly F, Lortholary A, et al. Neoadjuvant chemotherapy with or without nintedanib for advanced epithelial ovarian cancer: Lessons from the GINECO double-blind randomized phase II CHIVA trial. Gynecol Oncol. 2023;170:186–94.
pubmed: 36706645
doi: 10.1016/j.ygyno.2023.01.008
Luo W, Zeng Z, Jin Y, Yang L, Fan T, Wang Z, et al. Distinct immune microenvironment of lung adenocarcinoma in never-smokers from smokers. Cell Rep Med. 2023;4: 101078.
pubmed: 37301197
pmcid: 10313938
doi: 10.1016/j.xcrm.2023.101078
Gandham SK, Rao M, Shah A, Trivedi MS, Amiji MM. Combination microRNA-based cellular reprogramming with paclitaxel enhances therapeutic efficacy in a relapsed and multidrug-resistant model of epithelial ovarian cancer. Mol Ther Oncolytics. 2022;25:57–68.
pubmed: 35399604
pmcid: 8971728
doi: 10.1016/j.omto.2022.03.005
Price JC, Azizi E, Naiche LA, Parvani JG, Shukla P, Kim S, et al. Notch3 signaling promotes tumor cell adhesion and progression in a murine epithelial ovarian cancer model. PLoS ONE. 2020;15: e0233962.
pubmed: 32525899
pmcid: 7289394
doi: 10.1371/journal.pone.0233962
Udumula MP, Singh H, Rashid F, Poisson L, Tiwari N, Dimitrova I, et al. Intermittent fasting induced ketogenesis inhibits mouse epithelial ovarian cancer by promoting antitumor T cell response. iScience. 2023;26:107839.
pubmed: 37822507
pmcid: 10562806
doi: 10.1016/j.isci.2023.107839
Kodama J, Hashimoto I, Seki N, Hongo A, Yoshinouchi M, Okuda H, et al. Thrombospondin-1 and -2 messenger RNA expression in epithelial ovarian tumor. Anticancer Res. 2001;21:2983–7.
pubmed: 11712798
Alvarez AA, Axelrod JR, Whitaker RS, Isner PD, Bentley RC, Dodge RK, et al. Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients. Gynecol Oncol. 2001;82:273–8.
pubmed: 11531279
doi: 10.1006/gyno.2001.6287
Farokhi Boroujeni S, Rodriguez G, Galpin K, Yakubovich E, Murshed H, Ibrahim D, et al. BRCA1 and BRCA2 deficient tumour models generate distinct ovarian tumour microenvironments and differential responses to therapy. J Ovarian Res. 2023;16:231.
pubmed: 38017453
pmcid: 10683289
doi: 10.1186/s13048-023-01313-z
Willingham SB, Volkmer J-P, Gentles AJ, Sahoo D, Dalerba P, Mitra SS, et al. The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A. 2012;109:6662–7.
pubmed: 22451913
pmcid: 3340046
doi: 10.1073/pnas.1121623109
Tan M, Zhu L, Zhuang H, Hao Y, Gao S, Liu S, et al. Lewis Y antigen modified CD47 is an independent risk factor for poor prognosis and promotes early ovarian cancer metastasis. Am J Cancer Res. 2015;5:2777–87.
pubmed: 26609483
pmcid: 4633904
Yu L, Ding Y, Wan T, Deng T, Huang H, Liu J. Significance of CD47 and Its Association With Tumor Immune Microenvironment Heterogeneity in Ovarian Cancer. Front Immunol. 2021;12: 768115.
pubmed: 34966389
pmcid: 8710451
doi: 10.3389/fimmu.2021.768115
Mahdi H, Ni Y. Immunogenomic signatures to predict outcome in ovarian and endometrial cancers: Potential strategies in targeting the tumor immune microenvironment to improve response to immunotherapy. JCO. 2020;38:4–4.
doi: 10.1200/JCO.2020.38.5_suppl.4
Luo X, Mo J, Zhang M, Huang W, Bao Y, Zou R, et al. CD47—a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features. World J Surg Onc. 2024;22:44.
doi: 10.1186/s12957-024-03308-6
Liu R, Wei H, Gao P, Yu H, Wang K, Fu Z, et al. CD47 promotes ovarian cancer progression by inhibiting macrophage phagocytosis. Oncotarget. 2017;8:39021–32.
pubmed: 28380460
pmcid: 5503592
doi: 10.18632/oncotarget.16547
Masadah R, Ikram D, Riadi R, Tangdiung Y, Nelwan B, Ghaznawie M, et al. CD133, CD47, and PD-L1 Expression in Ovarian High-grade Serous Carcinoma and Its Association with Metastatic Disease: A Cross-sectional Study. Asian Pac J Cancer Prev. 2024;25:249–55.
pubmed: 38285791
pmcid: 10911714
doi: 10.31557/APJCP.2024.25.1.249
Samanta D, Park Y, Ni X, Li H, Zahnow CA, Gabrielson E, et al. Chemotherapy induces enrichment of CD47
Leary A, Genestie C, Blanc-Durand F, Gouy S, Dunant A, Maulard A, et al. Neoadjuvant chemotherapy alters the balance of effector to suppressor immune cells in advanced ovarian cancer. Cancer Immunol Immunother. 2021;70:519–31.
pubmed: 32852603
doi: 10.1007/s00262-020-02670-0
Logtenberg MEW, Jansen JHM, Raaben M, Toebes M, Franke K, Brandsma AM, et al. Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy. Nat Med. 2019;25:612–9.
pubmed: 30833751
pmcid: 7025889
doi: 10.1038/s41591-019-0356-z
Periyasamy A, Gopisetty G, Subramanium MJ, Velusamy S, Rajkumar T. Identification and validation of differential plasma proteins levels in epithelial ovarian cancer. J Proteomics. 2020;226: 103893.
pubmed: 32634479
doi: 10.1016/j.jprot.2020.103893
Cymbaluk-Płoska A, Chudecka-Głaz A, Pius-Sadowska E, Machaliński B, Menkiszak J. Thrombospondin-I concentrations behavior in plasma of patients with ovarian cancer. Cancer Biomark. 2017;20:31–9.
pubmed: 28655131
doi: 10.3233/CBM-161546
Pinessi D, Ostano P, Borsotti P, Bello E, Guffanti F, Bizzaro F, et al. Expression of thrombospondin-1 by tumor cells in patient-derived ovarian carcinoma xenografts. Connect Tissue Res. 2015;56:355–63.
pubmed: 25943461
doi: 10.3109/03008207.2015.1045065
Al-Sudani H, Ni Y, Jones P, Karakilic H, Cui L, Johnson LDS, et al. Targeting CD47-SIRPa axis shows potent preclinical anti-tumor activity as monotherapy and synergizes with PARP inhibition. NPJ Precis Oncol. 2023;7:69.
pubmed: 37468567
pmcid: 10356752
doi: 10.1038/s41698-023-00418-4
US FDA puts Gilead Sciences blood cancer drug studies on hold. Available from: https://www.reuters.com/business/healthcare-pharmaceuticals/us-fda-puts-gilead-sciences-blood-cancer-drug-studies-hold-2023-08-21/
Gilead ends phase 3 leukemia trial early after data disappoint, dealing another blow to $4.9B bet. Available from: https://www.fiercebiotech.com/biotech/gilead-ends-phase-3-leukemia-trial-early-after-data-disappoint-dealing-another-blow-49b-bet
Floquet N, Dedieu S, Martiny L, Dauchez M, Perahia D. Human thrombospondin’s (TSP-1) C-terminal domain opens to interact with the CD-47 receptor: a molecular modeling study. Arch Biochem Biophys. 2008;478:103–9.
pubmed: 18675774
doi: 10.1016/j.abb.2008.07.015
Mehta AK, Cheney EM, Hartl CA, Pantelidou C, Oliwa M, Castrillon JA, et al. Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. Nat Cancer. 2021;2:66–82.
pubmed: 33738458
doi: 10.1038/s43018-020-00148-7
Alvarez Secord A, O’Malley DM, Sood AK, Westin SN, Liu JF. Rationale for combination PARP inhibitor and antiangiogenic treatment in advanced epithelial ovarian cancer: A review. Gynecol Oncol. 2021;162:482–95.
pubmed: 34090705
doi: 10.1016/j.ygyno.2021.05.018
Liu Y, Xue R, Duan X, Shang X, Wang M, Wang F, et al. PARP inhibition synergizes with CD47 blockade to promote phagocytosis by tumor-associated macrophages in homologous recombination-proficient tumors. Life Sci. 2023;326: 121790.
pubmed: 37211345
doi: 10.1016/j.lfs.2023.121790
Wang L, Wang D, Sonzogni O, Ke S, Wang Q, Thavamani A, et al. PARP-inhibition reprograms macrophages toward an anti-tumor phenotype. Cell Rep. 2022;41: 111462.
pubmed: 36223740
pmcid: 9727835
doi: 10.1016/j.celrep.2022.111462