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21.04.2017 | Original Article

Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity

verfasst von: Kosuke Kawaguchi, Eiji Suzuki, Mariko Nishie, Isao Kii, Tatsuki R. Kataoka, Masahiro Hirata, Masashi Inoue, Fengling Pu, Keiko Iwaisako, Moe Tsuda, Ayane Yamaguchi, Hironori Haga, Masatoshi Hagiwara, Masakazu Toi

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 9/2017

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Abstract

Neuropilin-1 (NRP-1)-expressing macrophages are engaged in antitumor immune functions via various mechanisms. In this study, we investigated the role of NRP-1 on macrophages in antibody-mediated tumoricidal activity. Treatment of macrophages with NRP-1 knockdown or an anti-NRP-1-neutralizing antibody significantly suppressed antibody-dependent cellular cytotoxicity and modulated cytokine secretion from macrophages in vitro. Furthermore, in vivo studies using a humanized mouse model bearing human epidermal growth factor receptor-2 (HER2)-positive breast cancer xenografts showed that antibody-mediated antitumor activity and tumor infiltration of CD4⁺ T lymphocytes were significantly downregulated when peripheral blood mononuclear cells in which NRP-1 was knocked down were co-administered with an anti-HER2 antibody. These results revealed that NRP-1 expressed on macrophages plays an important role in antibody-mediated antitumor immunity. Taken together, the induction of NRP-1 on macrophages may be a therapeutic indicator for antibody treatments that exert antibody-dependent cellular cytotoxicity activity, although further studies are needed in order to support this hypothesis.

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Bellati F, Napoletano C, Ruscito I, Liberati M, Panici PB, Nuti M (2010) Cellular adaptive immune system plays a crucial role in trastuzumab clinical efficacy. J Clin Oncol 28:e369–e370. doi:10.1200/JCO.2010.28.6922 (author reply e71) CrossRefPubMed

Ferris RL, Jaffee EM, Ferrone S (2010) Tumor antigen-targeted, monoclonal antibody-based immunotherapy: clinical response, cellular immunity, and immunoescape. J Clin Oncol 28:4390–4399. doi:10.1200/JCO.2009.27.6360 CrossRefPubMedPubMedCentral

Park S, Jiang Z, Mortenson ED et al (2010) The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell 18:160–170. doi:10.1016/j.ccr.2010.06.014 CrossRefPubMedPubMedCentral

Stagg J, Loi S, Divisekera U, Ngiow SF, Duret H, Yagita H, Teng MW, Smyth MJ (2011) Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci USA 108:7142–7147. doi:10.1073/pnas.1016569108 CrossRefPubMedPubMedCentral

Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672CrossRefPubMed

Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4:71–78. doi:10.1038/nrc1256 CrossRefPubMed

Leek RD, Lewis CE, Whitehouse R, Greenall M, Clarke J, Harris AL (1996) Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res 56:4625–4629PubMed

Gwak JM, Jang MH, Kim DI, Seo AN, Park SY (2015) Prognostic value of tumor-associated macrophages according to histologic locations and hormone receptor status in breast cancer. PLoS One 10:e0125728. doi:10.1371/journal.pone.0125728 CrossRefPubMedPubMedCentral

Casazza A, Laoui D, Wenes M et al (2013) Impeding Macrophage Entry into Hypoxic Tumor Areas by Sema3A/Nrp1 Signaling Blockade Inhibits Angiogenesis and Restores Antitumor Immunity. Cancer Cell 24:695–709. doi:10.1016/j.ccr.2013.11.007 CrossRefPubMed

10.

Carrer A, Moimas S, Zacchigna S et al (2012) Neuropilin-1 identifies a subset of bone marrow Gr1- monocytes that can induce tumor vessel normalization and inhibit tumor growth. Cancer Res 72:6371–6381. doi:10.1158/0008-5472.CAN-12-0762 CrossRefPubMed

11.

Tordjman R, Lepelletier Y, Lemarchandel V, Cambot M, Gaulard P, Hermine O, Romeo PH (2002) A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response. Nat Immunol 3:477–482. doi:10.1038/ni789 PubMed

12.

Ji JD, Park-Min KH, Ivashkiv LB (2009) Expression and function of semaphorin 3A and its receptors in human monocyte-derived macrophages. Hum Immunol 70:211–217. doi:10.1016/j.humimm.2009.01.026 CrossRefPubMedPubMedCentral

13.

Takamatsu H, Takegahara N, Nakagawa Y et al (2010) Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin II. Nat Immunol 11:594–600. doi:10.1038/ni.1885 CrossRefPubMedPubMedCentral

14.

Broussas M, Broyer L, Goetsch L (2013) Evaluation of antibody-dependent cell cytotoxicity using lactate dehydrogenase (LDH) measurement. Methods Mol Biol 988:305–317. doi:10.1007/978-1-62703-327-5_19 CrossRefPubMed

15.

Wurdinger T, Badr C, Pike L, de Kleine R, Weissleder R, Breakefield XO, Tannous BA (2008) A secreted luciferase for ex vivo monitoring of in vivo processes. Nat Methods 5:171–173. doi:10.1038/nmeth.1177 CrossRefPubMedPubMedCentral

16.

Chung E, Yamashita H, Au P, Tannous BA, Fukumura D, Jain RK (2009) Secreted Gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases. PLoS One 4:e8316. doi:10.1371/journal.pone.0008316 CrossRefPubMedPubMedCentral

17.

Tannous BA (2009) Gaussia luciferase reporter assay for monitoring biological processes in culture and in vivo. Nat Protoc 4:582–591. doi:10.1038/nprot.2009.28 CrossRefPubMedPubMedCentral

18.

Salgado R, Denkert C, Demaria S et al (2014) Harmonization of the evaluation of tumor infiltrating lymphocytes (TILs) in breast cancer: recommendations by an international TILs-working group 2014. Ann Oncol. doi:10.1093/annonc/mdu450

19.

Valabrega G, Montemurro F, Aglietta M (2007) Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol 18:977–984. doi:10.1093/annonc/mdl475 CrossRefPubMed

20.

Flieger D, Spengler U, Beier I, Kleinschmidt R, Hoff A, Varvenne M, Sauerbruch T, Schmidt-Wolf I (1999) Enhancement of antibody dependent cellular cytotoxicity (ADCC) by combination of cytokines. Hybridoma 18:63–68. doi:10.1089/hyb.1999.18.63 CrossRefPubMed

21.

Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, Nakahata T (2003) Complete reconstitution of human lymphocytes from cord blood CD34⁺ cells using the NOD/SCID/γcnull mice model. Blood 102:873–880. doi:10.1182/blood-2002-09-2755 CrossRefPubMed

22.

Ito A, Ishida T, Yano H et al (2009) Defucosylated anti-CCR4 monoclonal antibody exercises potent ADCC-mediated antitumor effect in the novel tumor-bearing humanized NOD/Shi-scid, IL-2Rgamma(null) mouse model. Cancer Immunol Immunother 58:1195–1206. doi:10.1007/s00262-008-0632-0 CrossRefPubMed

23.

Denkert C, von Minckwitz G, Brase JC et al (2015) Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol 33:983–991. doi:10.1200/JCO.2014.58.1967 CrossRefPubMed

24.

Shaw GM, Levy PC, LoBuglio AF (1978) Human monocyte antibody-dependent cell-mediated cytotoxicity to tumor cells. J Clin Investig 62:1172–1180. doi:10.1172/JCI109236 CrossRefPubMedPubMedCentral

25.

Wallerius M, Wallmann T, Bartish M et al (2016) Guidance molecule SEMA3A restricts tumor growth by differentially regulating the proliferation of tumor-associated macrophages. Cancer Res 76:3166–3178. doi:10.1158/0008-5472.CAN-15-2596 CrossRefPubMed

26.

Denkert C, Loibl S, Noske A et al (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:105–113. doi:10.1200/JCO.2009.23.7370 CrossRefPubMed

27.

Loi S, Michiels S, Salgado R et al (2014) Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol 25:1544–1550. doi:10.1093/annonc/mdu112 CrossRefPubMed

28.

Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD (2002) IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168:3195–3204CrossRefPubMed

29.

Wu L, Adams M, Carter T, Chen R, Muller G, Stirling D, Schafer P, Bartlett JB (2008) Lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20⁺ tumor cells. Clin Cancer Res 14:4650–4657. doi:10.1158/1078-0432.CCR-07-4405 CrossRefPubMed

30.

Donia M, Hansen M, Sendrup SL, Iversen TZ, Ellebaek E, Andersen MH, Straten P, Svane IM (2013) Methods to improve adoptive T-cell therapy for melanoma: IFN-gamma enhances anticancer responses of cell products for infusion. J Invest Dermatol 133:545–552. doi:10.1038/jid.2012.336 CrossRefPubMed

31.

Friedman KM, Prieto PA, Devillier LE, Gross CA, Yang JC, Wunderlich JR, Rosenberg SA, Dudley ME (2012) Tumor-specific CD4⁺ melanoma tumor-infiltrating lymphocytes. J Immunother 35:400–408. doi:10.1097/CJI.0b013e31825898c5 CrossRefPubMed

32.

Quezada SA, Simpson TR, Peggs KS et al (2010) Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. J Exp Med 207:637–650. doi:10.1084/jem.20091918 CrossRefPubMedPubMedCentral

Titel: Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity
verfasst von: Kosuke Kawaguchi
Eiji Suzuki
Mariko Nishie
Isao Kii
Tatsuki R. Kataoka
Masahiro Hirata
Masashi Inoue
Fengling Pu
Keiko Iwaisako
Moe Tsuda
Ayane Yamaguchi
Hironori Haga
Masatoshi Hagiwara
Masakazu Toi
Publikationsdatum: 21.04.2017
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 9/2017
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-017-2002-2

Springer Medizin

Downregulation of neuropilin-1 on macrophages modulates antibody-mediated tumoricidal activity

Abstract

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Springer Medizin

Abstract

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