Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer

OncoImmunology

Volumn 6, Issue 8, 2017, Pages

  Sarhan, Dhifaf ^a,b   Leijonhufvud, Caroline ^a   Murray, Shannon ^c   Witt, Kristina ^a   Seitz, Christina ^a   Wallerius, Majken ^a   Xie, Hanjing ^a   Ullén, Anders ^a   Harmenberg, Ulrika ^a   Lidbrink, Elisabet ^a   Rolny, Charlotte ^a   Andersson, John ^a   Lundqvist, Andreas ^a,c  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b UNIVERSITY OF MINNESOTA   (United States)

^c NOVA SOUTHEASTERN UNIVERSITY   (United States)

Author keywords

Ca2+ calcineurin NFAT pathway; cancer patients; NK and T cell function; regulatory T cells; Zoledronic acid

Indexed keywords

CALCIUM CHANNEL; TRANSCRIPTION FACTOR NFAT; TRANSCRIPTOME; ZOLEDRONIC ACID;

ARTICLE; CELL ISOLATION; CELL PROLIFERATION; CHROMIUM RELEASE ASSAY; CLINICAL ARTICLE; CONFOCAL MICROSCOPY; CONTROLLED STUDY; FLOW CYTOMETRY; GENE EXPRESSION; HUMAN; IMMUNE RESPONSE; METASTASIS; REGULATORY T LYMPHOCYTE; RNA SEQUENCE;

EID: 85025139018     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2017.1338238     Document Type: Article

References (45)

1. Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC. Regulatory T cells in cancer. Adv Cancer Res 2010; 107:57-117; PMID:20399961; https://doi.org/10.1016/S0065-230X(10)07003-X
2. Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment:Expect the unexpected. J Clin Invest 2015; 125:3356-64; PMID:26168215; https://doi.org/10.1172/JCI80005
3. Beyer M, Schultze JL. Regulatory T cells in cancer. Blood 2006; 108:804-11; PMID:16861339; https://doi.org/10.1182/blood-2006-02-002774
4. Sun S, Fei X, Mao Y, Wang X, Garfield DH, Huang O, Wang J, Yuan F, Sun L, Yu Q, et al. PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients. Cancer Immunol Immunother 2014; 63:395-406; PMID:24514954; https://doi.org/10.1007/s00262-014-1519-x
5. Idorn M, Kollgaard T, Kongsted P, Sengelov L, Thor Straten P. Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer. Cancer Immunol Immunother 2014; 63:1177-87; PMID:25085000; https://doi.org/10.1007/s00262-014-1591-2
6. Liotta F, Gacci M, Frosali F, Querci V, Vittori G, Lapini A, Santarlasci V, Serni S, Cosmi L, Maggi L, et al. Frequency of regulatory T cells in peripheral blood and in tumour-infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma. BJU Int 2011; 107:1500-6; PMID:20735382; https://doi.org/10.1111/j.1464-410X.2010.09555.x
7. Jie HB, Schuler PJ, Lee SC, Srivastava RM, Argiris A, Ferrone S, Whiteside TL, Ferris RL. CTLA-4(+) Regulatory T cells increased in cetuximab-treated head and neck cancer patients suppress NK cell cytotoxicity and correlate with poor prognosis. Cancer Res 2015; 75:2200-10; PMID:25832655; https://doi.org/10.1158/0008-5472.CAN-14-2788
8. Liu JY, Li F, Wang LP, Chen XF, Wang D, Cao L, Ping Y, Zhao S, Li B, Thorne SH, et al. CTL- vs Treg lymphocyte-attracting chemokines, CCL4 and CCL20, are strong reciprocal predictive markers for survival of patients with oesophageal squamous cell carcinoma. Br J Cancer 2015; 113:747-55; PMID:26284335; https://doi.org/10.1038/bjc.2015.290
9. Gobel A, Thiele S, Browne AJ, Rauner M, Zinna VM, Hofbauer LC, Rachner TD. Combined inhibition of the mevalonate pathway with statins and zoledronic acid potentiates their anti-tumor effects in human breast cancer cells. Cancer Lett 2016; 375:162-71; PMID:26968247; https://doi.org/10.1016/j.canlet.2016.03.004
10. Okegawa T, Higaki M, Matsumoto T, Kase H, Murata A, Noda K, Noda H, Asaoka H, Oshi M, Tomoishi J, et al. Zoledronic acid improves clinical outcomes in patients with bone metastatic hormone-naive prostate cancer in a multicenter clinical trial. Anticancer Res 2014; 34:4415-20; PMID:25075079.
11. Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Zheng M, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004; 96:879-82; PMID:15173273; https://doi.org/10.1093/jnci/djh141
12. Aapro M, Abrahamsson PA, Body JJ, Coleman RE, Colomer R, Costa L, Crinò L, Dirix L, Gnant M, Gralow J, et al. Guidance on the use of bisphosphonates in solid tumours:Recommendations of an international expert panel. Ann Oncol 2008; 19:420-32; PMID:17906299; https://doi.org/10.1093/annonc/mdm442
13. Uemura H, Yanagisawa M, Ikeda I, Fujinami K, Iwasaki A, Noguchi S, Noguchi K, Kubota Y; Yokohama Bone Metastasis Study Group. Possible anti-tumor activity of initial treatment with zoledronic acid with hormonal therapy for bone-metastatic prostate cancer in multicenter clinical trial. Int J Clin Oncol 2013; 18:472-7; PMID:22491982; https://doi.org/10.1007/s10147-012-0406-8
14. Early Breast Cancer Trialists' Collaborative G, Coleman R, Powles T, Paterson A, Gnant M, Anderson S, Diel I, Gralow J, von Minckwitz G, Moebus V, et al. Adjuvant bisphosphonate treatment in early breast cancer:Meta-analyses of individual patient data from randomised trials. Lancet 2015; 386:1353-61; PMID:26211824; https://doi.org/10.1016/S0140-6736(15)60908-4
15. Nussbaumer O, Gruenbacher G, Gander H, Komuczki J, Rahm A, Thurnher M. Essential requirements of zoledronate-induced cytokine and gammadelta T cell proliferative responses. J Immunol 2013; 191:1346-55; https://doi.org/10.4049/jimmunol.1300603
16. Kondo M, Izumi T, Fujieda N, Kondo A, Morishita T, Matsushita H, Kakimi K. Expansion of human peripheral blood gammadelta T cells using zoledronate. J Vis Exp 2011; PMID:21931292; https://doi.org/10.3791/3182
17. Kondo M, Sakuta K, Noguchi A, Ariyoshi N, Sato K, Sato S, Sato K, Hosoi A, Nakajima J, Yoshida Y, et al. Zoledronate facilitates large-scale ex vivo expansion of functional gammadelta T cells from cancer patients for use in adoptive immunotherapy. Cytotherapy 2008; 10:842-56; PMID:19016372; https://doi.org/10.1080/14653240802419328
18. Mahtani R, Khan R, Jahanzeb M. The potential application of zoledronic acid as anticancer therapy in patients with non-small-cell lung cancer. Clin Lung Cancer 2011; 12:26-32; PMID:21273176; https://doi.org/10.3816/CLC.2011.n.003
19. Muraro M, Mereuta OM, Carraro F, Madon E, Fagioli F. Osteosarcoma cell line growth inhibition by zoledronate-stimulated effector cells. Cell Immunol 2007; 249:63-72; PMID:18163982; https://doi.org/10.1016/j.cellimm.2007.11.005
20. Sarhan D, D'Arcy P, Wennerberg E, Liden M, Hu J, Winqvist O, Rolny C, Lundqvist A. Activated monocytes augment TRAIL-mediated cytotoxicity by human NK cells through release of IFN-gamma. Eur J Immunol 2013; 43:249-57; PMID:22996291; https://doi.org/10.1002/eji.201242735
21. Comito G, Segura CP, Taddei ML, Lanciotti M, Serni S, Morandi A, et al. Zoledronic acid impairs stromal reactivity by inhibiting M2-macrophages polarization and prostate cancer-associated fibroblasts. Oncotarget 2016; https://doi.org/10.18632/oncotarget.9497
22. Castella B, Riganti C, Fiore F, Pantaleoni F, Canepari ME, Peola S, et al. Immune modulation by zoledronic acid in human myeloma:An advantageous cross-talk between Vgamma9Vdelta2 T cells, alphabeta CD8+ T cells, regulatory T cells, and dendritic cells. J Immunol 2011; 187:1578-90; https://doi.org/10.4049/jimmunol.1002514
23. Liu H, Wang SH, Chen SC, Chen CY, Lo JL, Lin TM. Immune modulation of CD4+CD25+ regulatory T cells by zoledronic acid. BMC Immunol 2016; 17:45; PMID:27887569; https://doi.org/10.1186/s12865-016-0183-7
24. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR:Ultrafast universal RNA-seq aligner. Bioinformatics 2013; 29:15-21; PMID:23104886; https://doi.org/10.1093/bioinformatics/bts635
25. Robinson MD, McCarthy DJ, Smyth GK. edgeR:A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010; 26:139-40; PMID:19910308; https://doi.org/10.1093/bioinformatics/btp616
26. Ligtenberg MA, Mougiakakos D, Mukhopadhyay M, Witt K, Lladser A, Chmielewski M, Riet T, Abken H, Kiessling R. Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress-induced loss of antitumor activity. J Immunol 2016; 196:759-66; PMID:26673145; https://doi.org/10.4049/jimmunol.1401710
27. Oh-hora M, Rao A. The calcium/NFAT pathway:Role in development and function of regulatory T cells. Microbes Infect 2009; 11:612-9; PMID:19375514; https://doi.org/10.1016/j.micinf.2009.04.008
28. Wu Y, Borde M, Heissmeyer V, Feuerer M, Lapan AD, Stroud JC, Bates DL, Guo L, Han A, Ziegler SF, et al. FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 2006; 126:375-87; PMID:16873067; https://doi.org/10.1016/j.cell.2006.05.042
29. Hu H, Djuretic I, Sundrud MS, Rao A. Transcriptional partners in regulatory T cells:Foxp3, Runx and NFAT. Trends Immunol 2007; 28:329-32; PMID:17618833; https://doi.org/10.1016/j.it.2007.06.006
30. Marie JC, Letterio JJ, Gavin M, Rudensky AY. TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells. J Exp Med 2005; 201:1061-7; PMID:15809351; https://doi.org/10.1084/jem.20042276
31. Islas-Vazquez L, Prado-Garcia H, Aguilar-Cazares D, Meneses-Flores M, Galicia-Velasco M, Romero-Garcia S, Camacho-Mendoza C, Lopez-Gonzalez JS. LAP TGF-Beta Subset of CD4(+)CD25(+)CD127(-) treg cells is increased and overexpresses LAP TGF-beta in lung adenocarcinoma patients. BioMed Res Int 2015; 2015:430943; PMID:26582240; https://doi.org/10.1155/2015/430943
32. Saito T, Nishikawa H, Wada H, Nagano Y, Sugiyama D, Atarashi K, Maeda Y, Hamaguchi M, Ohkura N, Sato E, et al. Two FOXP3(+)CD4(+) T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med 2016; 22:679-84; PMID:27111280; https://doi.org/10.1038/nm.4086
33. Zhou H, Chen L, You Y, Zou L, Zou P. Foxp3-transduced polyclonal regulatory T cells suppress NK cell functions in a TGF-beta dependent manner. Autoimmunity 2010; 43:299-307; PMID:20166879; https://doi.org/10.3109/08916930903405875
34. Wang G, Khattar M, Guo Z, Miyahara Y, Linkes SP, Sun Z, He X, Stepkowski SM, Chen W. IL-2-deprivation and TGF-beta are two non-redundant suppressor mechanisms of CD4+CD25+ regulatory T cell which jointly restrain CD4+CD25- cell activation. Immunol Lett 2010; 132:61-8; PMID:20570629; https://doi.org/10.1016/j.imlet.2010.06.001
35. Sharma R, Zheng L, Deshmukh US, Jarjour WN, Sung SS, Fu SM, Ju ST. A regulatory T cell-dependent novel function of CD25 (IL-2Ralpha) controlling memory CD8(+) T cell homeostasis. J Immunol 2007; 178:1251-5; PMID:17237369; https://doi.org/10.4049/jimmunol.178.3.1251
36. Gasteiger G, Hemmers S, Firth MA, Le Floc'h A, Huse M, Sun JC, Rudensky AY. IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells. J Exp Med 2013; 210:1167-78; PMID:23650441; https://doi.org/10.1084/jem.20122462
37. Zhou J, You W, Sun G, Li Y, Chen B, Ai J, et al. The Marine-Derived oligosaccharide sulfate MS80, a novel TGF-beta1 inhibitor, reverses TGF-beta1-induced epithelial-mesenchymal transition and suppresses tumor metastasis. J Pharmacol Exp Ther 2016; https://doi.org/10.1124/jpet.116.234799
38. Morris JC, Tan AR, Olencki TE, Shapiro GI, Dezube BJ, Reiss M, Hsu FJ, Berzofsky JA, Lawrence DP. Phase I study of GC1008 (fresolimumab):A human anti-transforming growth factor-beta (TGFbeta) monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma. PloS One 2014; 9:e90353; PMID:24618589; https://doi.org/10.1371/journal.pone.0090353
39. Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A, Lewis D, Hippen K, et al. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 2014; 123:3855-63; PMID:24719405; https://doi.org/10.1182/blood-2013-10-532531
40. Rech AJ, Mick R, Martin S, Recio A, Aqui NA, Powell DJ, Jr, Colligon TA, Trosko JA, Leinbach LI, Pletcher CH, et al. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci Transl Med 2012; 4:134ra62; PMID:22593175; https://doi.org/10.1126/scitranslmed.3003330
41. Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 2007; 56:641-8; PMID:16960692; https://doi.org/10.1007/s00262-006-0225-8
42. Ganguly B, Balasa B, Efros L, Hinton PR, Hartman S, Thakur A, et al. The CD25-binding antibody daclizumab high-yield process has a distinct glycosylation pattern and reduced antibody-dependent cell-mediated cytotoxicity in comparison to Zenapax(R). mAbs 2016:0.
43. Colleoni M, Gray KP, Gelber S, Lang I, Thurlimann B, Gianni L, et al. Low-dose oral cyclophosphamide and methotrexate maintenance for hormone receptor-negative early breast cancer:International Breast Cancer Study Group Trial 22-00. J Clin Oncol 2016; https://doi.org/10.1200/JCO.2015.65.6595
44. Zeiser R, Nguyen VH, Beilhack A, Buess M, Schulz S, Baker J, Contag CH, Negrin RS. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 2006; 108:390-9; PMID:16522809; https://doi.org/10.1182/blood-2006-01-0329
45. Fukushima K, Ikehara Y, Yamashita K. Functional role played by the glycosylphosphatidylinositol anchor glycan of CD48 in interleukin-18-induced interferon-gamma production. J Biol Chem 2005; 280:18056-62; PMID:15760905; https://doi.org/10.1074/jbc.M413297200