Doxorubicin pretreatment enhances FAPα/survivin co-targeting DNA vaccine anti-tumor activity primarily through decreasing peripheral MDSCs in the 4T1 murine breast cancer model

References

• Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252–14. doi:10.1038/nrc3239.
   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 Engl J Med. 2012;366(26):2443–2454. doi:10.1056/NEJMoa1200690.
   PubMed Web of Science ®Google Scholar
• Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–571. doi:10.1038/nature13954.
   PubMed Web of Science ®Google Scholar
• Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science (New York, NY). 2006;313(5795):1960–1964. doi:10.1126/science.1129139.
   Google Scholar
• Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, Ellis IO, Green AR. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J clin oncol. 2011;29(15):1949–1955. doi:10.1200/JCO.2010.30.5037.
   PubMed Web of Science ®Google Scholar
• Li J, Wang J, Chen R, Bai Y, Lu X. The prognostic value of tumor-infiltrating T lymphocytes in ovarian cancer. Oncotarget. 2017;8(9):15621–15631. doi:10.18632/oncotarget.14919.
   PubMedGoogle Scholar
• Xu X, Tan Y, Qian Y, Xue W, Wang Y, Du J, Jin L, Ding W. Clinicopathologic and prognostic significance of tumor-infiltrating CD8+ T cells in patients with hepatocellular carcinoma: a meta-analysis. Medicine. 2019;98(2):e13923. doi:10.1097/MD.0000000000013923.
   PubMed Web of Science ®Google Scholar
• van der Burg SH, Arens R, Ossendorp F, van Hall T, Melief CJ. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat Rev Cancer. 2016;16(4):219–233. doi:10.1038/nrc.2016.16.
   PubMed Web of Science ®Google Scholar
• Finn OJ. The dawn of vaccines for cancer prevention. Nat Rev Immunol. 2018;18(3):183–194. doi:10.1038/nri.2017.140.
   PubMed Web of Science ®Google Scholar
• Brouty-Boye D. Developmental biology of fibroblasts and neoplastic disease. Prog Mol Subcell Biol. 2005;40:55–77.
   PubMedGoogle Scholar
• Ostman A, Augsten M. Cancer-associated fibroblasts and tumor growth–bystanders turning into key players. Curr Opin Genet Dev. 2009;19(1):67–73. doi:10.1016/j.gde.2009.01.003.
   PubMed Web of Science ®Google Scholar
• Shiga K, Hara M, Nagasaki T, Sato T, Takahashi H, Takeyama H. Cancer-associated fibroblasts: their characteristics and their roles in tumor growth. Cancers (Basel). 2015;7(4):2443–2458. doi:10.3390/cancers7040902.
   PubMed Web of Science ®Google Scholar
• Williams SA, Harata-Lee Y, Comerford I, Anderson RL, Smyth MJ, McColl SR. Multiple functions of CXCL12 in a syngeneic model of breast cancer. Mol Cancer. 2010;9(1):250. doi:10.1186/1476-4598-9-250.
   PubMedGoogle Scholar
• Ouyang L, Chang W, Fang B, Qin J, Qu X, Cheng F. Estrogen-induced SDF-1alpha production promotes the progression of ER-negative breast cancer via the accumulation of MDSCs in the tumor microenvironment. Sci Rep. 2016;6(1):39541. doi:10.1038/srep39541.
   PubMedGoogle Scholar
• Yang X, Lin Y, Shi Y, Li B, Liu W, Yin W, Dang Y, Chu Y, Fan J, He R. FAP promotes immunosuppression by cancer-associated fibroblasts in the tumor microenvironment via STAT3-CCL2 signaling. Cancer Res. 2016;76(14):4124–4135. doi:10.1158/0008-5472.CAN-15-2973.
   PubMed Web of Science ®Google Scholar
• Geng F, Guo J, Guo QQ, Xie Y, Dong L, Zhou Y, Liu CL, Yu B, Wu H, Wu JX, et al. A DNA vaccine expressing an optimized secreted FAPalpha induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer. Vaccine. 2019;37(31):4382–4391. doi:10.1016/j.vaccine.2019.06.012.
   PubMed Web of Science ®Google Scholar
• Fassnacht M, Lee J, Milazzo C, Boczkowski D, Su Z, Nair S, Gilboa E. Induction of CD4(+) and CD8(+) T-cell responses to the human stromal antigen, fibroblast activation protein: implication for cancer immunotherapy. Clin Cancer Rese. 2005;11(15):5566–5571. doi:10.1158/1078-0432.CCR-05-0699.
   PubMed Web of Science ®Google Scholar
• Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008;8(1):61–70. doi:10.1038/nrc2293.
   PubMed Web of Science ®Google Scholar
• Andersen MH, Pedersen LO, Capeller B, Brocker EB, Becker JC, Thor Straten P. Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients. Cancer Res. 2001;61:5964–5968.
   PubMed Web of Science ®Google Scholar
• Rohayem J, Diestelkoetter P, Weigle B, Oehmichen A, Schmitz M, Mehlhorn J, Conrad K, Rieber EP. Antibody response to the tumor-associated inhibitor of apoptosis protein survivin in cancer patients. Cancer Res. 2000;60(7):1815–1817.
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–174. doi:10.1038/nri2506.
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI. Myeloid-derived suppressor cells. Cancer Immunol Res. 2017;5(1):3–8. doi:10.1158/2326-6066.CIR-16-0297.
   PubMed Web of Science ®Google Scholar
• Groth C, Hu X, Weber R, Fleming V, Altevogt P, Utikal J, Umansky V. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer. 2019;120(1):16–25. doi:10.1038/s41416-018-0333-1.
   PubMed Web of Science ®Google Scholar
• Bunt SK, Sinha P, Clements VK, Leips J, Ostrand-Rosenberg S. Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression. J Immunol. 2006;176(1):284–290. doi:10.4049/jimmunol.176.1.284.
   PubMed Web of Science ®Google Scholar
• Youn JI, Nagaraj S, Collazo M, Gabrilovich DI. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol. 2008;181(8):5791–5802. doi:10.4049/jimmunol.181.8.5791.
   PubMed Web of Science ®Google Scholar
• Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166(1):678–689. doi:10.4049/jimmunol.166.1.678.
   PubMed Web of Science ®Google Scholar
• Jin G, Zhang Y, Chang X, Zhang Y, Xu J, Wei M, Zeng X. Increased percentage of mo-MDSCs in human peripheral blood may be a potential indicator in the diagnosis of breast cancer. Oncol Res Treat. 2017;40(10):603–608. doi:10.1159/000478933.
   PubMed Web of Science ®Google Scholar
• Le HK, Graham L, Cha E, Morales JK, Manjili MH, Bear HD. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol. 2009;9(7–8):900–909. doi:10.1016/j.intimp.2009.03.015.
   PubMed Web of Science ®Google Scholar
• Vincent J, Mignot G, Chalmin F, Ladoire S, Bruchard M, Chevriaux A, Martin F, Apetoh L, Rebe C, Ghiringhelli F, et al. 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res. 2010;70(8):3052–3061. doi:10.1158/0008-5472.CAN-09-3690.
   PubMed Web of Science ®Google Scholar
• Alizadeh D, Trad M, Hanke NT, Larmonier CB, Janikashvili N, Bonnotte B, Katsanis E, Larmonier N. Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer. Cancer Res. 2014;74(1):104–118. doi:10.1158/0008-5472.CAN-13-1545.
   PubMed Web of Science ®Google Scholar
• Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 2013;65(2):157–170. doi:10.1111/j.2042-7158.2012.01567.x.
   PubMed Web of Science ®Google Scholar
• Alizadeh D, Katsanis E, Larmonier N. Chemotherapeutic targeting of myeloid-derived suppressor cells. Oncoimmunology. 2014;3(1):e27359. doi:10.4161/onci.27359.
   PubMed Web of Science ®Google Scholar
• Duperret EK, Trautz A, Ammons D, Perales-Puchalt A, Wise MC, Yan J, Reed C, Weiner DB. Alteration of the tumor stroma using a consensus dna vaccine targeting fibroblast activation protein (FAP) synergizes with antitumor vaccine therapy in Mice. Clin Cancer Rese. 2018;24(5):1190–1201. doi:10.1158/1078-0432.CCR-17-2033.
   PubMed Web of Science ®Google Scholar
• Zhang H, Wang Y, Liu C, Zhang L, Xia Q, Zhang Y, Wu J, Jiang C, Chen Y, Wu Y, et al. DNA and adenovirus tumor vaccine expressing truncated survivin generates specific immune responses and anti-tumor effects in a murine melanoma model. Cancer Immunol Immunother. 2012;61(10):1857–1867. doi:10.1007/s00262-012-1296-3.
   PubMed Web of Science ®Google Scholar
• Rong Y, Yuan C-H, Qu Z, Zhou H, Guan Q, Yang N, Leng X-H, Bu L, Wu K, Wang F-B, et al. Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing PGE2. Sci Rep. 2016;6(1):23824. doi:10.1038/srep23824.
   PubMedGoogle Scholar
• Kawano M, Tanaka K, Itonaga I, Iwasaki T, Miyazaki M, Ikeda S, TSUMURA H. Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma. Oncol Lett. 2016;11(3):2169–2175. doi:10.3892/ol.2016.4175.
   PubMed Web of Science ®Google Scholar
• Nam G-H, Lee EJ, Kim YK, Hong Y, Choi Y, Ryu M-J, Woo J, Cho Y, Ahn DJ, Yang Y, et al. Combined Rho-kinase inhibition and immunogenic cell death triggers and propagates immunity against cancer. Nat Commun. 2018;9(1):2165. doi:10.1038/s41467-018-04607-9.
   Web of Science ®Google Scholar
• Vacchelli E, Aranda F, Eggermont A, Galon J, Sautes-Fridman C, Cremer I, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: chemotherapy with immunogenic cell death inducers. Oncoimmunology. 2014;3(3):e27878. doi:10.4161/onci.27878.
   PubMed Web of Science ®Google Scholar
• Tang H, Wang Y, Chlewicki LK, Zhang Y, Guo J, Liang W, Wang J, Wang X, Fu YX. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade. Cancer Cell. 2016;30(3):500. doi:10.1016/j.ccell.2016.08.011.
   Google Scholar
• Houthuijzen JM, Jonkers J. Cancer-associated fibroblasts as key regulators of the breast cancer tumor microenvironment. Cancer Metastasis Rev. 2018;37(4):577–597. doi:10.1007/s10555-018-9768-3.
   PubMed Web of Science ®Google Scholar
• Turley SJ, Cremasco V, Astarita JL. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol. 2015;15(11):669–682. doi:10.1038/nri3902.
   PubMed Web of Science ®Google Scholar
• Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science (New York, NY). 2010;330(6005):827–830. doi:10.1126/science.1195300.
   Google Scholar
• Xia Q, Zhang FF, Geng F, Liu CL, Xu P, Lu ZZ, Yu B, Wu H, Wu JX, Zhang HH, et al. Anti-tumor effects of DNA vaccine targeting human fibroblast activation protein alpha by producing specific immune responses and altering tumor microenvironment in the 4T1 murine breast cancer model. Cancer Immunol Immunother. 2016;65(5):613–624. doi:10.1007/s00262-016-1827-4.
   PubMed Web of Science ®Google Scholar
• Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA. Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One. 2009;4(11):e7965. doi:10.1371/journal.pone.0007965.
   PubMed Web of Science ®Google Scholar
• Loeffler M, Kruger JA, Niethammer AG, Reisfeld RA. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J Clin Invest. 2006;116(7):1955–1962. doi:10.1172/JCI26532.
   PubMed Web of Science ®Google Scholar
• Zhu K, Qin H, Cha SC, Neelapu SS, Overwijk W, Lizee GA, Abbruzzese JL, Hwu P, Radvanyi L, Kwak LW, et al. Survivin DNA vaccine generated specific antitumor effects in pancreatic carcinoma and lymphoma mouse models. Vaccine. 2007;25(46):7955–7961. doi:10.1016/j.vaccine.2007.08.050.
   PubMed Web of Science ®Google Scholar
• Feng S, Cheng X, Zhang L, Lu X, Chaudhary S, Teng R, Frederickson C, Champion MM, Zhao R, Cheng L, et al. Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers. Proc Natl Acad Sci U S A. 2018;115(40):10094–10099. doi:10.1073/pnas.1800695115.
   PubMed Web of Science ®Google Scholar
• Lu J, Liu X, Liao YP, Wang X, Ahmed A, Jiang W, Ji Y, Meng H, Nel AE. Breast cancer chemo-immunotherapy through liposomal delivery of an immunogenic cell death stimulus plus interference in the IDO-1 pathway. ACS Nano. 2018;12(11):11041–11061. doi:10.1021/acsnano.8b05189.
   PubMed Web of Science ®Google Scholar
• Wang JC, Sun X, Ma Q, Fu GF, Cong LL, Zhang H, Fan DF, Feng J, Lu SY, Liu JL, et al. Metformin’s antitumour and anti-angiogenic activities are mediated by skewing macrophage polarization. J Cell Mol Med. 2018;22(8):3825–3836. doi:10.1111/jcmm.13655.
   Web of Science ®Google Scholar
• Welters MJ, van der Sluis TC, van Meir H, Loof NM, van Ham VJ, van Duikeren S, Santegoets SJ, Arens R, de Kam ML, Cohen AF, et al. Vaccination during myeloid cell depletion by cancer chemotherapy fosters robust T cell responses. Sci Transl Med. 2016;8(334):334ra52. doi:10.1126/scitranslmed.aad8307.
   PubMed Web of Science ®Google Scholar
• Domingos-Pereira S, Galliverti G, Hanahan D, Nardelli-Haefliger D. Carboplatin/paclitaxel, E7-vaccination and intravaginal CpG as tri-therapy towards efficient regression of genital HPV16 tumors. J Immunother Cancer. 2019;7(1):122. doi:10.1186/s40425-019-0593-1.
   PubMed Web of Science ®Google Scholar
• Jang HY, Han BS, Kwon B, Sin JI. Optimized gemcitabine therapy in combination with E7 peptide immunization elicits tumor cure by preventing ag-specific ctl inhibition in animals with large established tumors. DNA Cell Biol. 2018;37(10):850–860. doi:10.1089/dna.2018.4319.
   PubMed Web of Science ®Google Scholar
• Tallon de Lara P, Cecconi V, Hiltbrunner S, Yagita H, Friess M, Bode B, Opitz I, Vrugt B, Weder W, Stolzmann P, et al. Gemcitabine synergizes with immune checkpoint inhibitors and overcomes resistance in a preclinical model and mesothelioma patients. Clin Cancer Rese. 2018;24(24):6345–6354. doi:10.1158/1078-0432.CCR-18-1231.
   PubMed Web of Science ®Google Scholar
• Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich P-Y, Mendrzyk R, et al. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012;18(8):1254–1261. doi:10.1038/nm.2883.
   PubMed Web of Science ®Google Scholar
• Son CH, Bae JH, Lee HR, Shin DY, Yang K, Park YS. Enhanced dendritic cell-based immunotherapy using low-dose cyclophosphamide and CD25-targeted antibody for transplanted Lewis lung carcinoma cells. J Immunother (Hagerstown, Md: 1997). 2015;38(3):107–115. doi:10.1097/CJI.0000000000000068.
   PubMed Web of Science ®Google Scholar
• Xia Q, Geng F, Zhang FF, Liu CL, Xu P, Lu ZZ, Xie Y, Sun B, Wu H, Yu B, et al. Cyclophosphamide enhances anti-tumor effects of a fibroblast activation protein alpha-based DNA vaccine in tumor-bearing mice with murine breast carcinoma. Immunopharmacol Immunotoxicol. 2017;39(1):37–44. doi:10.1080/08923973.2016.1269337.
   PubMed Web of Science ®Google Scholar