Inhibition of Hedgehog signaling reprograms the dysfunctional immune microenvironment in breast cancer

References

• Mao Y, Keller ET, Garfield DH, Shen K, Wang J. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 2013;32(1–2):303–315. DOI: 10.1007/s10555-012-9415-3.
   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
• Varol C, Mildner A, Jung S. Macrophages: development and tissue specialization. Annu Rev Immunol. 2015;33:643–675. DOI: 10.1146/annurev-immunol-032414-112220.
   PubMed Web of Science ®Google Scholar
• Obeid E, Nanda R, Fu YX, Olopade OI. The role of tumor-associated macrophages in breast cancer progression (review). Int J Oncol. 2013;43(1):5–12. DOI: 10.3892/ijo.2013.1938.
   PubMed Web of Science ®Google Scholar
• Das A, Sinha M, Datta S, Abas M, Chaffee S, Sen CK, Roy S. Monocyte and macrophage plasticity in tissue repair and regeneration. Am J Pathol. 2015;185(10):2596–2606. DOI: 10.1016/j.ajpath.2015.06.001.
   PubMed Web of Science ®Google Scholar
• Chen JJ, Lin YC, Yao PL, Yuan A, Chen HY, Shun CT, Tsai MF, Chen CH, Yang PC. Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol. 2005;23(5):953–964. DOI: 10.1200/JCO.2005.12.172.
   PubMed Web of Science ®Google Scholar
• Williams CB, Yeh ES, Soloff AC. Tumor-associated macrophages: unwitting accomplices in breast cancer malignancy. NPJ Breast Cancer. 2016;2DOI: 10.1038/npjbcancer.2015.25.
   PubMed Web of Science ®Google Scholar
• Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012;122(3):787–795. DOI: 10.1172/JCI59643.
   PubMed Web of Science ®Google Scholar
• Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014;6:13. DOI: 10.12703/P6-13.
   PubMedGoogle Scholar
• Kroner A, Greenhalgh AD, Zarruk JG. Dos Santos RP, Gaestel M, David S. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron. 2014;83(5):1098–1116. DOI: 10.1016/j.neuron.2014.07.027.
   PubMed Web of Science ®Google Scholar
• Genin M, Clement F, Fattaccioli A, Raes M, Michiels C. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide. BMC Cancer. 2015;15:577. DOI: 10.1186/s12885-015-1546-9.
   PubMed Web of Science ®Google Scholar
• Veremeyko T, Siddiqui S, Sotnikov I, Yung A, Ponomarev ED. IL-4/IL-13-dependent and independent expression of miR-124 and its contribution to M2 phenotype of monocytic cells in normal conditions and during allergic inflammation. PLoS ONE. 2013;8(12):e81774. DOI: 10.1371/journal.pone.0081774.
   PubMed Web of Science ®Google Scholar
• Martinez-Nunez RT, Louafi F, Sanchez-Elsner T. The interleukin 13 (IL-13) pathway in human macrophages is modulated by microRNA-155 via direct targeting of interleukin 13 receptor alpha1 (IL13Ralpha1). J Biol Chem. 2011;286(3):1786–1794. DOI: 10.1074/jbc.M110.169367.
   PubMed Web of Science ®Google Scholar
• Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity. 2016;44(3):450–462. DOI: 10.1016/j.immuni.2016.02.015.
   PubMed Web of Science ®Google Scholar
• Lesterhuis WJ, Punt CJ, Hato SV, Eleveld-Trancikova D, Jansen BJ, Nierkens S, Schreibelt G, de Boer A, Van Herpen CM, Kaanders JH, et al. Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice. J Clin Invest. 2011;121(8):3100–3108. DOI: 10.1172/JCI43656.
   PubMed Web of Science ®Google Scholar
• Fukushi J, Ono M, Morikawa W, Iwamoto Y, Kuwano M. The activity of soluble VCAM-1 in angiogenesis stimulated by IL-4 and IL-13. J Immunol. 2000;165(5):2818–2823.
   PubMed Web of Science ®Google Scholar
• Zhang QW, Liu L, Gong CY, Shi HS, Zeng YH, Wang XZ, Zhao YW, Wei YQ. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS ONE. 2012;7(12):e50946. DOI: 10.1371/journal.pone.0050946.
   PubMed Web of Science ®Google Scholar
• Niino D, Komohara Y, Murayama T, Aoki R, Kimura Y, Hashikawa K, Kiyasu J, Takeuchi M, Suefuji N, Sugita Y, et al. Ratio of M2 macrophage expression is closely associated with poor prognosis for Angioimmunoblastic T-cell lymphoma (AITL). Pathol Int. 2010;60(4):278–283. DOI: 10.1111/j.1440-1827.2010.02514.x.
   PubMed Web of Science ®Google Scholar
• Medrek C, Ponten F, Jirstrom K, Leandersson K. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer. 2012;12:306. DOI: 10.1186/1471-2407-12-306.
   PubMed Web of Science ®Google Scholar
• Casazza A, Laoui D, Wenes M, Rizzolio S, Bassani N, Mambretti M, Deschoemaeker S, Van Ginderachter JA, Tamagnone L, Mazzone M. Impeding macrophage entry into hypoxic tumor areas by Sema3A/Nrp1 signaling blockade inhibits angiogenesis and restores antitumor immunity. Cancer Cell. 2013;24(6):695–709. DOI: 10.1016/j.ccr.2013.11.007.
   PubMed Web of Science ®Google Scholar
• Laoui D, Van Overmeire E, Di Conza G, Aldeni C, Keirsse J, Morias Y, Movahedi K, Houbracken I, Schouppe E, Elkrim Y, et al. Tumor hypoxia does not drive differentiation of tumor-associated macrophages but rather fine-tunes the M2-like macrophage population. Cancer Res. 2014;74(1):24–30. DOI: 10.1158/0008-5472.CAN-13-1196.
   PubMed Web of Science ®Google Scholar
• Jiang J, Hui CC. Hedgehog signaling in development and cancer. Dev Cell. 2008;15(6):801–812. DOI: 10.1016/j.devcel.2008.11.010.
   PubMed Web of Science ®Google Scholar
• Harris LG, Samant RS, Shevde LA. Hedgehog signaling: networking to nurture a promalignant tumor microenvironment. Mol Cancer Res. 2011;9(9):1165–1174. DOI: 10.1158/1541-7786.MCR-11-0175.
   PubMed Web of Science ®Google Scholar
• Hanna A, Shevde LA. Hedgehog signaling: modulation of cancer properies and tumor mircroenvironment. Mol Cancer. 2016;15:24. DOI: 10.1186/s12943-016-0509-3.
   PubMed Web of Science ®Google Scholar
• Das S, Samant RS, Shevde LA. Nonclassical activation of Hedgehog signaling enhances multidrug resistance and makes cancer cells refractory to smoothened-targeting Hedgehog inhibition. J Biol Chem. 2013;288(17):11824–11833. DOI: 10.1074/jbc.M112.432302.
   PubMed Web of Science ®Google Scholar
• Yoo YA, Kang MH, Lee HJ, Kim BH, Park JK, Kim HK, Kim JS, Oh SC. Sonic hedgehog pathway promotes metastasis and lymphangiogenesis via activation of Akt, EMT, and MMP-9 pathway in gastric cancer. Cancer Res. 2011;71(22):7061–7070. DOI: 10.1158/0008-5472.CAN-11-1338.
   PubMed Web of Science ®Google Scholar
• Das S, Tucker JA, Khullar S, Samant RS, Shevde LA. Hedgehog signaling in tumor cells facilitates osteoblast-enhanced osteolytic metastases. PLoS ONE. 2012;7(3):e34374. DOI: 10.1371/journal.pone.0034374.
   PubMed Web of Science ®Google Scholar
• Pereira TA, Xie G, Choi SS, Syn WK, Voieta I, Lu J, Chan IS, Swiderska M, Amaral KB, Antunes CM, et al. Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni. Liver Int. 2013;33(1):149–161. DOI: 10.1111/liv.12016.
   PubMed Web of Science ®Google Scholar
• Sousa S, Brion R, Lintunen M, Kronqvist P, Sandholm J, Monkkonen J, Kellokumpu-Lehtinen PL, Lauttia S, Tynninen O, Joensuu H, et al. Human breast cancer cells educate macrophages toward the M2 activation status. Breast Cancer Res. 2015;17:101. DOI: 10.1186/s13058-015-0621-0.
   PubMed Web of Science ®Google Scholar
• Heppner GH, Miller FR, Shekhar PM. Nontransgenic models of breast cancer. Breast Cancer Res. 2000;2(5):331–334.
   PubMed Web of Science ®Google Scholar
• Maun HR, Wen X, Lingel A, de Sauvage FJ, Lazarus RA, Scales SJ, Hymowitz SG. Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site. J Biol Chem. 2010;285(34):26570–26580. DOI: 10.1074/jbc.M110.112284.
   PubMed Web of Science ®Google Scholar
• Jimenez-Garcia L, Herranz S, Luque A, Hortelano S. Critical role of p38 MAPK in IL-4-induced alternative activation of peritoneal macrophages. Eur J Immunol. 2015;45(1):273–286. DOI: 10.1002/eji.201444806.
   PubMed Web of Science ®Google Scholar
• Khaled WT, Read EK, Nicholson SE, Baxter FO, Brennan AJ, Came PJ, Sprigg N, McKenzie AN, Watson CJ. The IL-4/IL-13/Stat6 signalling pathway promotes luminal mammary epithelial cell development. Development. 2007;134(15):2739–2750. DOI: 10.1242/dev.003194.
   PubMed Web of Science ®Google Scholar
• Nolan-Stevaux O, Lau J, Truitt ML, Chu GC, Hebrok M, Fernandez-Zapico ME, Hanahan D. GLI1 is regulated through smoothened-independent mechanisms in neoplastic pancreatic ducts and mediates PDAC cell survival and transformation. Genes Dev. 2009;23(1):24–36. DOI: 10.1101/gad.1753809.
   PubMed Web of Science ®Google Scholar
• Damhofer H, Medema JP, Veenstra VL, Badea L, Popescu I, Roelink H, Bijlsma MF. Assessment of the stromal contribution to Sonic Hedgehog-dependent pancreatic adenocarcinoma. Mol Oncol. 2013;7(6):1031–1042. DOI: 10.1016/j.molonc.2013.08.004.
   PubMed Web of Science ®Google Scholar
• Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, Gordon S, Hamilton JA, Ivashkiv LB, Lawrence T, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20. DOI: 10.1016/j.immuni.2014.06.008.
   PubMed Web of Science ®Google Scholar
• Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000;164(12):6166–6173.
   PubMed Web of Science ®Google Scholar
• Linde N, Casanova-Acebes M, Sosa MS, Mortha A, Rahman A, Farias E, Harper K, Tardio E, Reyes Torres I, Jones J, et al. Macrophages orchestrate breast cancer early dissemination and metastasis. Nat Commun. 2018;9(1):21. DOI: 10.1038/s41467-017-02481-5.
   PubMed Web of Science ®Google Scholar
• Lim SY, Yuzhalin AE, Gordon-Weeks AN, Muschel RJ. Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget. 2016;7(19):28697–28710. DOI: 10.18632/oncotarget.7376.
   PubMedGoogle Scholar
• Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J, Wang-Gillam A, Goedegebuure SP, Linehan DC, DeNardo DG. CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models. Cancer Res. 2014;74(18):5057–5069. DOI: 10.1158/0008-5472.CAN-13-3723.
   PubMed Web of Science ®Google Scholar
• Vonderheide RH, Glennie MJ. Agonistic CD40 antibodies and cancer therapy. Clin Cancer Res. 2013;19(5):1035–1043. DOI: 10.1158/1078-0432.CCR-12-2064.
   PubMed Web of Science ®Google Scholar
• Genard G, Lucas S, Michiels C. Reprogramming of tumor-associated macrophages with anticancer therapies: radiotherapy versus chemo- and immunotherapies. Front Immunol. 2017;8:828. DOI: 10.3389/fimmu.2017.00828.
   PubMed Web of Science ®Google Scholar
• Furmanski AL, Barbarulo A, Solanki A, Lau CI, Sahni H, Saldana JI, D’Acquisto F, Crompton T. The transcriptional activator Gli2 modulates T-cell receptor signalling through attenuation of AP-1 and NFkappaB activity. J Cell Sci. 2015;128(11):2085–2095. DOI: 10.1242/jcs.165803.
   PubMed Web of Science ®Google Scholar
• Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U.S.A. 2010;107(9):4275–4280. DOI: 10.1073/pnas.0915174107.
   PubMed Web of Science ®Google Scholar
• van Rooijen N, Hendrikx E. Liposomes for specific depletion of macrophages from organs and tissues. Methods Mol Biol. 2010;605:189–203. DOI: 10.1007/978-1-60327-360-2_13.
   PubMedGoogle Scholar
• Rowbotham NJ, Hager-Theodorides AL, Furmanski AL, Crompton T. A novel role for Hedgehog in T-cell receptor signaling: implications for development and immunity. Cell Cycle. 2007;6(17):2138–2142. DOI: 10.4161/cc.6.17.4644.
   PubMed Web of Science ®Google Scholar
• Rowbotham NJ, Hager-Theodorides AL, Furmanski AL, Ross SE, Outram SV, Dessens JT, Crompton T. Sonic hedgehog negatively regulates pre-TCR-induced differentiation by a Gli2-dependent mechanism. Blood. 2009;113(21):5144–5156. DOI: 10.1182/blood-2008-10-185751.
   PubMed Web of Science ®Google Scholar
• Outram SV, Hager-Theodorides AL, Shah DK, Rowbotham NJ, Drakopoulou E, Ross SE, Lanske B, Dessens JT, Crompton T. Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation. Blood. 2009;113(10):2217–2228. DOI: 10.1182/blood-2008-03-144840.
   PubMed Web of Science ®Google Scholar
• Stewart GA, Lowrey JA, Wakelin SJ, Fitch PM, Lindey S, Dallman MJ, Lamb JR, Howie SE. Sonic hedgehog signaling modulates activation of and cytokine production by human peripheral CD4+ T cells. J Immunol. 2002;169(10):5451–5457.
   PubMed Web of Science ®Google Scholar
• Sethi N, Dai X, Winter CG, Kang Y. Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell. 2011;19(2):192–205. DOI: 10.1016/j.ccr.2010.12.022.
   PubMed Web of Science ®Google Scholar
• Aslakson CJ, Miller FR. Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res. 1992;52(6):1399–1405.
   PubMed Web of Science ®Google Scholar
• Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–2120. DOI: 10.1093/bioinformatics/btu170.
   PubMed Web of Science ®Google Scholar
• 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(1):15–21. DOI: 10.1093/bioinformatics/bts635.
   PubMed Web of Science ®Google Scholar
• Bullard JH, Purdom E, Hansen KD, Dudoit S. Evaluation of statistical methods for normalization and differential expression in mRNA-Seq experiments. BMC Bioinformatics. 2010;11:94. DOI: 10.1186/1471-2105-11-94.
   PubMed Web of Science ®Google Scholar
• Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U.S.A. 2005;102(43):15545–15550. DOI: 10.1073/pnas.0506580102.
   PubMed Web of Science ®Google Scholar
• Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–273. DOI: 10.1038/ng1180.
   PubMed Web of Science ®Google Scholar
• Wong HAB, West KA, Pacheco P, La H, Januario T, Yauch RL, de Sauvage FJ, Gould SE. Pharmacokinetic–pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation. Clin Cancer Res. 2011;17(14):4682–4692. DOI: 10.1158/1078-0432.CCR-11-0975.
   PubMed Web of Science ®Google Scholar