nach oben

Breast Cancer Research and Treatment

Erschienen in:

01.08.2015 | Preclinical study

Poly (I: C) modulates the immunosuppressive activity of myeloid-derived suppressor cells in a murine model of breast cancer

verfasst von: Parvin Forghani, Edmund K. Waller

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Polyinosinic-polycytidylic acid [Poly (I: C)], a ligand for Toll-like receptor (TLR-3), is used as an adjuvant to enhance anti-tumor immunity because of its prominent effects on CD8 T cells and NK cells. Myeloid-derived suppressor cells (MDSCs) are one of the main immunosuppressive factors in cancer, and their abnormal accumulation is correlated with the clinical stage of breast cancer and is an important mechanism of tumor immune evasion. Although Poly (I: C) is thought to have direct anti-tumor activity in different cell lines, its effect on immunosuppressive MDSCs in tumor-bearing animals has not been studied. 4T1-Luc, a metastatic breast cancer mouse cell line, was injected into the left flank of female BALB/c mice. Tumor-bearing mice were treated with i.p. injection of Poly (I: C) or PBS beginning on day 7 after tumor inoculation. WBCs and MDSCs were counted using coulter counter and stained for flow cytometry, respectively. Bioluminescent imaging was used to monitor tumor burden at multiple time points during the course of tumor growth. Poly (I: C) treatment led to a decrease in MDSC frequencies in BM, blood, and tumor compared to saline-treated control mice. Poly (I: C) treatment also abrogated the immunosuppressive function of MDSCs, concomitant with an increase in local T cell response of the immune system in a murine model of breast cancer. Poly (I: C) treatment decreases MDSC frequency and immunosuppressive function in 4T1-tumor-bearing hosts and effectively augments the activity of breast cancer immunotherapy.

Nur mit Berechtigung zugänglich

Zoglmeier C, Bauer H, Norenberg D, Wedekind G, Bittner P, Sandholzer N, Rapp M, Anz D, Endres S, Bourquin C (2011) CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin Cancer Res 17(7):1765–1775CrossRefPubMed

Finke J (2011) MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic. Inter Immunopharmacol 11:856CrossRef

Nakamura H, Horai Y, Suzuki T, Okada A, Ichinose K, Yamasaki S, Koji T, Kawakami A (2013) TLR3-mediated apoptosis and activation of phosphorylated Akt in the salivary gland epithelial cells of primary Sjogren’s syndrome patients. Rheumatol Int 33(2):441–450CrossRefPubMed

Markowitz J, Wesolowski R, Papenfuss T, Brooks TR, Carson WE 3rd (2013) Myeloid-derived suppressor cells in breast cancer. Breast Cancer Res Treat 140(1):13–21PubMedCentralCrossRefPubMed

Harashima N, Inao T, Imamura R, Okano S, Suda T, Harada M (2012) Roles of the PI3 K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of human prostate cancer cells. Cancer Immunol Immunother 61(5):667–676CrossRefPubMed

Sun R, Zhang Y, Lv Q, Liu B, Jin M, Zhang W, He Q, Deng M, Liu X, Li G et al (2011) Toll-like receptor 3 (TLR3) induces apoptosis via death receptors and mitochondria by up-regulating the transactivating p63 isoform alpha (TAP63alpha). J Biol Chem 286(18):15918–15928PubMedCentralCrossRefPubMed

Taura M, Fukuda R, Suico MA, Eguma A, Koga T, Shuto T, Sato T, Morino-Koga S, Kai H (2010) TLR3 induction by anticancer drugs potentiates poly I:C-induced tumor cell apoptosis. Cancer Sci 101(7):1610–1617CrossRefPubMed

Liechtenstein T, Perez-Janices N, Gato M, Caliendo F, Kochan G, Blanco-Luquin I, Van der Jeught K, Arce F, Guerrero-Setas D, Fernandez-Irigoyen J et al (2014) A highly efficient tumor-infiltrating MDSC differentiation system for discovery of anti-neoplastic targets, which circumvents the need for tumor establishment in mice. Oncotarget 5(17):7843–7857PubMedCentralPubMed

Ghansah T (2012) A novel strategy for modulation of MDSC to enhance cancer immunotherapy. Oncoimmunology 1(6):984–985PubMedCentralCrossRefPubMed

10.

Mignot G, Chalmin F, Ladoire S, Rébé C, Ghiringhelli F (2011) Tumor exosome-mediated MDSC activation. Am J pathol 178(3):1403–1405PubMedCentralCrossRefPubMed

11.

Green TL, Santos MF, Ejaeidi AA, Craft BS, Lewis RE, Cruse JM (2014) Toll-like receptor (TLR) expression of immune system cells from metastatic breast cancer patients with circulating tumor cells. Exp Mol Pathol 97(1):44–48CrossRefPubMed

12.

Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49–59PubMedCentralCrossRefPubMed

13.

Chi N, Tan Z, Ma K, Bao L, Yun Z (2014) Increased circulating myeloid-derived suppressor cells correlate with cancer stages, interleukin-8 and -6 in prostate cancer. Int J Clin Exp Med 7(10):3181–3192PubMedCentralPubMed

14.

Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176(8):4894–4901CrossRefPubMed

15.

Cheng YS, Xu F (2010) Anticancer function of polyinosinic-polycytidylic acid. Cancer Biol Ther 10(12):1219–1223CrossRefPubMed

16.

Forghani P, Khorramizadeh MR, Waller EK (2014) Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer. Cancer Med 3(2):215–224PubMedCentralCrossRefPubMed

17.

Ray A, Dittel BN (2010) Isolation of mouse peritoneal cavity cells. J Vis Exp 35:1488PubMed

18.

Forghani P, Harris W, Giver CR, Mirshafiey A, Galipeau J, Waller EK (2013) Properties of immature myeloid progenitors with nitric-oxide-dependent immunosuppressive activity isolated from bone marrow of tumor-free mice. PLoS ONE 8(7):e64837PubMedCentralCrossRefPubMed

19.

Ostrand-Rosenberg S, Sinha P, Chornoguz O, Ecker C (2012) Regulating the suppressors: apoptosis and inflammation govern the survival of tumor-induced myeloid-derived suppressor cells (MDSC). Cancer Immunol Immunother 61(8):1319–1325CrossRefPubMed

20.

Sinha P, Okoro C, Foell D, Freeze HH, Ostrand-Rosenberg S, Srikrishna G (2008) Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol 181(7):4666–4675PubMedCentralCrossRefPubMed

21.

Fucikova J, Rozkova D, Ulcova H, Budinsky V, Sochorova K, Pokorna K, Bartunkova J, Spisek R (2011) Poly I: C-activated dendritic cells that were generated in Cell Gro for use in cancer immunotherapy trials. J Trans Med 9:223CrossRef

22.

Verdijk RM, Mutis T, Esendam B, Kamp J, Melief CJ, Brand A, Goulmy E (1999) Polyriboinosinic polyribocytidylic acid (poly(I:C)) induces stable maturation of functionally active human dendritic cells. J Immunol 163(1):57–61PubMed

23.

Moller I, Michel K, Frech N, Burger M, Pfeifer D, Frommolt P, Veelken H, Thomas-Kaskel AK (2008) Dendritic cell maturation with poly(I:C)-based versus PGE2-based cytokine combinations results in differential functional characteristics relevant to clinical application. J Immunother 31(5):506–519CrossRefPubMed

24.

Nagaraj S, Nelson A, Youn JI, Cheng P, Quiceno D, Gabrilovich DI (2012) Antigen-specific CD4(+) T cells regulate function of myeloid-derived suppressor cells in cancer via retrograde MHC class II signaling. Cancer Res 72(4):928–938PubMedCentralCrossRefPubMed

25.

Kulbe H, Thompson R, Wilson JL, Robinson S, Hagemann T, Fatah R, Gould D, Ayhan A, Balkwill F (2007) The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Cancer Res 67(2):585–592PubMedCentralCrossRefPubMed

26.

Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schultheis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF et al (2009) The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest 119(10):3011–3023PubMedCentralCrossRefPubMed

27.

Salaun B, Zitvogel L, Asselin-Paturel C, Morel Y, Chemin K, Dubois C, Massacrier C, Conforti R, Chenard MP, Sabourin JC et al (2011) TLR3 as a biomarker for the therapeutic efficacy of double-stranded RNA in breast cancer. Cancer Res 71(5):1607–1614CrossRefPubMed

28.

Bunt SK, Clements VK, Hanson EM, Sinha P, Ostrand-Rosenberg S (2009) Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4. J Leukoc Biol 85(6):996–1004PubMedCentralCrossRefPubMed

29.

Conrad E, Resch TK, Gogesch P, Kalinke U, Bechmann I, Bogdan C, Waibler Z (2014) Protection against RNA-induced liver damage by myeloid cells requires type I interferon and IL-1 receptor antagonist in mice. Hepatology 59(4):1555–1563CrossRefPubMed

30.

Aranda F, Llopiz D, Diaz-Valdes N, Riezu-Boj JI, Bezunartea J, Ruiz M, Martinez M, Durantez M, Mansilla C, Prieto J et al (2011) Adjuvant combination and antigen targeting as a strategy to induce polyfunctional and high-avidity T-cell responses against poorly immunogenic tumors. Cancer Res 71(9):3214–3224CrossRefPubMed

31.

Paone A, Starace D, Galli R, Padula F, De Cesaris P, Filippini A, Ziparo E, Riccioli A (2008) Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism. Carcinogenesis 29(7):1334–1342CrossRefPubMed

32.

Forte G, Rega A, Morello S, Luciano A, Arra C, Pinto A, Sorrentino R (2012) Polyinosinic-polycytidylic acid limits tumor outgrowth in a mouse model of metastatic lung cancer. J Immunol 188(11):5357–5364CrossRefPubMed

33.

Shime H, Kojima A, Maruyama A, Saito Y, Oshiumi H, Matsumoto M, Seya T (2014) Myeloid-derived suppressor cells confer tumor-suppressive functions on natural killer cells via polyinosinic:polycytidylic acid treatment in mouse tumor models. J Innate Immun 6(3):293–305PubMed

34.

Ostrand-Rosenberg S, Sinha P, Beury DW, Clements VK (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22(4):275–281PubMedCentralCrossRefPubMed

35.

Dalotto-Moreno T, Croci DO, Cerliani JP, Martinez-Allo VC, Dergan-Dylon S, Mendez-Huergo SP, Stupirski JC, Mazal D, Osinaga E, Toscano MA et al (2013) Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Res 73(3):1107–1117CrossRefPubMed

36.

Kovacs-Solyom F, Blasko A, Fajka-Boja R, Katona RL, Vegh L, Novak J, Szebeni GJ, Krenacs L, Uher F, Tubak V et al (2010) Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1. Immunol Lett 127(2):108–118CrossRefPubMed

37.

Liu C, Zhang C, Lu H, Cai J, Wang Z, Chen J, Liu F, Wu Z, Liu X, Sun W (2011) Poly(I:C) induce bone marrow precursor cells into myeloid-derived suppressor cells. Mol Cell Biochem 358(1–2):317–323CrossRefPubMed

38.

Danilin S, Merkel AR, Johnson JR, Johnson RW, Edwards JR, Sterling JA (2012) Myeloid-derived suppressor cells expand during breast cancer progression and promote tumor-induced bone destruction. Oncoimmunology 1(9):1484–1494PubMedCentralCrossRefPubMed

Titel: Poly (I: C) modulates the immunosuppressive activity of myeloid-derived suppressor cells in a murine model of breast cancer
verfasst von: Parvin Forghani
Edmund K. Waller
Publikationsdatum: 01.08.2015
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2015
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3508-y

Springer Medizin

Poly (I: C) modulates the immunosuppressive activity of myeloid-derived suppressor cells in a murine model of breast cancer

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2015

Increased COX-2 expression in epithelial and stromal cells of high mammographic density tissues and in a xenograft model of mammographic density

Heat shock factor 1 induces cancer stem cell phenotype in breast cancer cell lines

Post-irradiation angiosarcoma of the breast: clinical presentation and outcome in a series of six cases

The prognostic value of the neoadjuvant response index in triple-negative breast cancer: validation and comparison with pathological complete response as outcome measure

Assessment of HER2 status in invasive breast cancers with increased centromere 17 copy number

Selection and evolution in the genomic landscape of copy number alterations in ductal carcinoma in situ (DCIS) and its progression to invasive carcinoma of ductal/no special type: a meta-analysis

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie