S100A4 blockage alleviates agonistic anti-CD137 antibody-induced liver pathology without disruption of antitumor immunity

References

• Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 2016; 13(6):394; PMID:27118494; https://doi.org/10.1038/nrclinonc.2016.65
   PubMed Web of Science ®Google Scholar
• Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Eng J Med 2010; 363(8):711-23; PMID:20525992; https://doi.org/10.1056/NEJMoa1003466
   PubMed Web of Science ®Google Scholar
• Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Eng J Med 2012; 366(26):2455-65; PMID:22658128; https://doi.org/10.1056/NEJMoa1200694
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Eng J Med 2012; 366(26):2443-54; PMID:22658127; https://doi.org/10.1056/NEJMoa1200690
   PubMed Web of Science ®Google Scholar
• Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest 2015; 125(9):3384-91; PMID:26325035; https://doi.org/10.1172/JCI80011
   PubMed Web of Science ®Google Scholar
• Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 2016; 16(5):275-87; PMID:27079802; https://doi.org/10.1038/nrc.2016.36
   PubMed Web of Science ®Google Scholar
• Sanmamed MF, Pastor F, Rodriguez A, Perez-Gracia JL, Rodriguez-Ruiz ME, Jure-Kunkel M, Melero I. Agonists of co-stimulation in cancer immunotherapy directed against CD137, OX40, GITR, CD27, CD28, and ICOS. Semin Oncol 2015; 42(4):640-55; PMID:26320067; https://doi.org/10.1053/j.seminoncol.2015.05.014
   PubMed Web of Science ®Google Scholar
• Niu L, Strahotin S, Hewes B, Zhang B, Zhang Y, Archer D et al. Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice. J Immunol 2007; 178(7):4194-213; PMID:17371976; https://doi.org/10.4049/jimmunol.178.7.4194
   PubMedGoogle Scholar
• Dubrot J, Milheiro F, Alfaro C, Palazon A, Martinez-Forero I, Perez-Gracia JL et al. Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ. Cancer Immunol Immunother 2010; 59(8):1223-33; PMID:20336294; https://doi.org/10.1007/s00262-010-0846-9
   PubMed Web of Science ®Google Scholar
• Croft M. Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat Rev Immunol 2003; 3(8):609-20; PMID:12974476; https://doi.org/10.1038/nri1148
   PubMed Web of Science ®Google Scholar
• Myers LM, Vella AT. Interfacing T-cell effector and regulatory function through CD137 (4-1BB) co-stimulation. Trends Immunol 2005; 26(8):440-6; PMID:15979409; https://doi.org/10.1016/j.it.2005.06.003
   PubMedGoogle Scholar
• Houot R, Goldstein MJ, Kohrt HE, Myklebust JH, Alizadeh AA, Lin JT, Irish JM, Torchia JA, Kolstad A, Chen L et al. Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion. Blood 2009; 114(16):3431-8; PMID:19641184; https://doi.org/10.1182/blood-2009-05-223958
   PubMed Web of Science ®Google Scholar
• Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, Mittler RS, Chen L. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med 1997; 3(6):682-5; PMID:9176498; https://doi.org/10.1038/nm0697-682
   PubMed Web of Science ®Google Scholar
• Homet Moreno B, Mok S, Comin-Anduix B, Hu-Lieskovan S, Ribas A. Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma. Oncoimmunology 2016; 5(7):e1052212; PMID:27622011; https://doi.org/10.1080/2162402X.2015.1052212
   PubMed Web of Science ®Google Scholar
• Narazaki H, Zhu Y, Luo L, Zhu G, Chen L. CD137 agonist antibody prevents cancer recurrence: contribution of CD137 on both hematopoietic and nonhematopoietic cells. Blood 2010; 115(10):1941-8; PMID:20068221; https://doi.org/10.1182/blood-2008-12-192591
   PubMedGoogle Scholar
• Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M, Smith JP, Walker AJ, Kohler ME, Venkateshwara VR et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med 2015; 21(6):581-90; PMID:25939063; https://doi.org/10.1038/nm.3838
   PubMed Web of Science ®Google Scholar
• Holohan DR, Lee JC, Bluestone JA. Shifting the evolving CAR T cell platform into higher gear. Cancer Cell 2015; 28(4):401-2; PMID:26461084; https://doi.org/10.1016/j.ccell.2015.09.014
   PubMedGoogle Scholar
• Ye Q, Song DG, Poussin M, Yamamoto T, Best A, Li C, Coukos G, Powell DJ Jr. CD137 accurately identifies and enriches for naturally occurring tumor-reactive T cells in tumor. Clin Cancer Res 2014; 20(1):44-55; PMID:24045181; https://doi.org/10.1158/1078-0432.CCR-13-0945
   PubMed Web of Science ®Google Scholar
• Chacon JA, Sarnaik AA, Pilon-Thomas S, Radvanyi L. Triggering co-stimulation directly in melanoma tumor fragments drives CD8+ tumor-infiltrating lymphocyte expansion with improved effector-memory properties. Oncoimmunology 2015; 4(12):e1040219; PMID:26587314; https://doi.org/10.1080/2162402X.2015.1040219
   PubMedGoogle Scholar
• Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol 2013; 13(4):227-42; PMID:23470321; https://doi.org/10.1038/nri3405
   PubMed Web of Science ®Google Scholar
• Sun Y, Chen HM, Subudhi SK, Chen J, Koka R, Chen L, Fu YX. Costimulatory molecule-targeted antibody therapy of a spontaneous autoimmune disease. Nat Med 2002; 8(12):1405-13; PMID:12426559; https://doi.org/10.1038/nm1202-796
   PubMedGoogle Scholar
• Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 2010; 37(5):508-16; PMID:21074066; https://doi.org/10.1053/j.seminoncol.2010.09.008
   PubMed Web of Science ®Google Scholar
• Segal NH, Logan TF, Hodi FS, McDermott DF, Melero I, Hamid O, Schmidt H, Robert C, Chiarion-Sileni V, Ascierto PA et al. Results from an integrated safety analysis of urelumab, an agonist anti-CD137 monoclonal antibody. Clin Cancer Res 2016; PMID:27756788; https://doi.org/10.1158/1078-0432.CCR-16-1272
   PubMedGoogle Scholar
• Wang J, Zhao W, Cheng L, Guo M, Li D, Li X, Tan Y, Ma S, Li S, Yang Y et al. CD137-mediated pathogenesis from chronic hepatitis to hepatocellular carcinoma in hepatitis B virus-transgenic mice. J Immunol 2010; 185(12):7654-62; PMID:21059892; https://doi.org/10.4049/jimmunol.1000927
   PubMedGoogle Scholar
• Wilcox RA, Flies DB, Wang H, Tamada K, Johnson AJ, Pease LR, Rodriguez M, Guo Y, Chen L. Impaired infiltration of tumor-specific cytolytic T cells in the absence of interferon-gamma despite their normal maturation in lymphoid organs during CD137 monoclonal antibody therapy. Cancer Res 2002; 62(15):4413-8; PMID:12154048
   PubMed Web of Science ®Google Scholar
• Boye K, Maelandsmo GM. S100A4 and metastasis: a small actor playing many roles. Am J Pathol 2010; 176(2):528-35; PMID:20019188; https://doi.org/10.2353/ajpath.2010.090526
   PubMedGoogle Scholar
• Mishra SK, Siddique HR, Saleem M. S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence. Cancer Metastasis Rev 2012; 31(1–2):163-72; PMID:22109080; https://doi.org/10.1007/s10555-011-9338-4
   PubMedGoogle Scholar
• Osterreicher CH, Penz-Osterreicher M, Grivennikov SI, Guma M, Koltsova EK, Datz C, Sasik R, Hardiman G, Karin M, Brenner DA. Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liver. Proc Natl Acad Sci U S A 2011; 108(1):308-13; PMID:21173249; https://doi.org/10.1073/pnas.1017547108
   PubMedGoogle Scholar
• Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE, Neilson EG. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 1995; 130(2):393-405; PMID:7615639; https://doi.org/10.1083/jcb.130.2.393
   PubMed Web of Science ®Google Scholar
• Zhang J, Chen L, Liu X, Kammertoens T, Blankenstein T, Qin Z. Fibroblast-specific protein 1/S100A4-positive cells prevent carcinoma through collagen production and encapsulation of carcinogens. Cancer Res 2013; 73(9):2770-81; PMID:23539447; https://doi.org/10.1158/0008-5472.CAN-12-3022
   PubMedGoogle Scholar
• Kim EJ, Helfman DM. Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. J Biol Chem 2003; 278(32):30063-73; PMID:12756252; https://doi.org/10.1074/jbc.M304909200
   PubMedGoogle Scholar
• Kiryushko D, Novitskaya V, Soroka V, Klingelhofer J, Lukanidin E, Berezin V, Bock E. Molecular mechanisms of Ca(2+) signaling in neurons induced by the S100A4 protein. Mol Cell Biol 2006; 26(9):3625-38; PMID:16612001; https://doi.org/10.1128/MCB.26.9.3625-3638.2006
   PubMedGoogle Scholar
• Liang J, Piao Y, Holmes L, Fuller GN, Henry V, Tiao N, de Groot JF. Neutrophils promote the malignant glioma phenotype through S100A4. Clin Cancer Res 2014; 20(1):187-98; PMID:24240114; https://doi.org/10.1158/1078-0432.CCR-13-1279
   PubMed Web of Science ®Google Scholar
• Dmytriyeva O, Pankratova S, Owczarek S, Sonn K, Soroka V, Ridley CM, Marsolais A, Lopez-Hoyos M, Ambartsumian N, Lukanidin E et al. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury. Nat Commun 2012; 3:1197; PMID:23149742; https://doi.org/10.1038/ncomms2202
   PubMed Web of Science ®Google Scholar
• Fabris L, Cadamuro M, Moserle L, Dziura J, Cong X, Sambado L, Nardo G, Sonzogni A, Colledan M, Furlanetto A et al. Nuclear expression of S100A4 calcium-binding protein increases cholangiocarcinoma invasiveness and metastasization. Hepatology 2011; 54(3):890-9; PMID:21618579; https://doi.org/10.1002/hep.24466
   PubMed Web of Science ®Google Scholar
• Grum-Schwensen B, Klingelhofer J, Grigorian M, Almholt K, Nielsen BS, Lukanidin E, Ambartsumian N. Lung metastasis fails in MMTV-PyMT oncomice lacking S100A4 due to a T-cell deficiency in primary tumors. Cancer Res 2010; 70(3):936-47; PMID:20103644; https://doi.org/10.1158/0008-5472.CAN-09-3220
   PubMedGoogle Scholar
• Schmidt-Hansen B, Ornas D, Grigorian M, Klingelhofer J, Tulchinsky E, Lukanidin E, Ambartsumian N. Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 2004; 23(32):5487-95; PMID:15122322; https://doi.org/10.1038/sj.onc.1207720
   PubMedGoogle Scholar
• Hansen MT, Forst B, Cremers N, Quagliata L, Ambartsumian N, Grum-Schwensen B, Klingelhofer J, Abdul-Al A, Herrmann P, Osterland M et al. A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4. Oncogene 2015; 34(4):424-35; PMID:24469032; https://doi.org/10.1038/onc.2013.568
   PubMed Web of Science ®Google Scholar
• Zhang J, Chen L, Xiao M, Wang C, Qin Z. FSP1+ fibroblasts promote skin carcinogenesis by maintaining MCP-1-mediated macrophage infiltration and chronic inflammation. Am J Pathol 2011; 178(1):382-90; PMID:21224075; https://doi.org/10.1016/j.ajpath.2010.11.017
   PubMedGoogle Scholar
• Chen L, Li J, Zhang J, Dai C, Liu X, Wang J, Gao Z, Guo H, Wang R, Lu S et al. S100A4 promotes liver fibrosis via activation of hepatic stellate cells. J Hepatol 2015; 62(1):156-64; PMID:25111176; https://doi.org/10.1016/j.jhep.2014.07.035
   PubMed Web of Science ®Google Scholar
• Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002; 110(3):341-50; PMID:12163453; https://doi.org/10.1172/JCI0215518
   PubMed Web of Science ®Google Scholar
• Iwano M, Fischer A, Okada H, Plieth D, Xue C, Danoff TM, Neilson EG. Conditional abatement of tissue fibrosis using nucleoside analogs to selectively corrupt DNA replication in transgenic fibroblasts. Mol Ther 2001; 3(2):149-59; PMID:11237671; https://doi.org/10.1006/mthe.2000.0251
   PubMedGoogle Scholar
• Salomon B, Maury S, Loubiere L, Caruso M, Onclercq R, Klatzmann D. A truncated herpes simplex virus thymidine kinase phosphorylates thymidine and nucleoside analogs and does not cause sterility in transgenic mice. Mol Cell Biol 1995; 15(10):5322-8; PMID:7565681; https://doi.org/10.1128/MCB.15.10.5322
   PubMedGoogle Scholar
• Xue C, Plieth D, Venkov C, Xu C, Neilson EG. The gatekeeper effect of epithelial-mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Res 2003; 63(12):3386-94; PMID:12810675
   PubMed Web of Science ®Google Scholar
• Heindryckx F, Colle I, Van Vlierberghe H. Experimental mouse models for hepatocellular carcinoma research. Int J Exp Pathol 2009; 90(4):367-86; PMID:19659896; https://doi.org/10.1111/j.1365-2613.2009.00656.x
   PubMed Web of Science ®Google Scholar
• Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Eng J Med 2006; 355(10):1018-28; PMID:16908486; https://doi.org/10.1056/NEJMoa063842
   PubMed Web of Science ®Google Scholar
• Zhu Y, Zhu G, Luo L, Flies AS, Chen L. CD137 stimulation delivers an antigen-independent growth signal for T lymphocytes with memory phenotype. Blood 2007; 109(11):4882-9; PMID:17244673; https://doi.org/10.1182/blood-2006-10-043463
   PubMedGoogle Scholar
• Crispe IN, Dao T, Klugewitz K, Mehal WZ, Metz DP. The liver as a site of T-cell apoptosis: graveyard, or killing field? Immunol Rev 2000; 174:47-62; PMID:10807506; https://doi.org/10.1034/j.1600-0528.2002.017412.x
   PubMed Web of Science ®Google Scholar
• Grum-Schwensen B, Klingelhofer J, Beck M, Bonefeld CM, Hamerlik P, Guldberg P, Grigorian M, Lukanidin E, Ambartsumian N. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance. BMC Cancer 2015; 15:44; PMID:25884510; https://doi.org/10.1186/s12885-015-1034-2
   PubMedGoogle Scholar
• McEver RP, Baenziger NL, Majerus PW. Isolation and quantitation of the platelet membrane glycoprotein deficient in thrombasthenia using a monoclonal hybridoma antibody. J Clin Invest 1980; 66(6):1311-8; PMID:6449521; https://doi.org/10.1172/JCI109983
   PubMedGoogle Scholar
• Kawada N, Kuroki T, Kobayashi K, Inoue M, Nakatani K, Kaneda K, Nagata K. Expression of heat-shock protein 47 in mouse liver. Cell Tissue Res 1996; 284(2):341-6; PMID:8625400; https://doi.org/10.1007/s004410050594
   PubMedGoogle Scholar
• Zhao X, Rong L, Zhao X, Li X, Liu X, Deng J, Wu H, Xu X, Erben U, Wu P et al. TNF signaling drives myeloid-derived suppressor cell accumulation. J Clin Invest 2012; 122(11):4094-104; PMID:23064360; https://doi.org/10.1172/JCI64115
   PubMed Web of Science ®Google Scholar