Toll-like receptor 7/8 agonist, R848, exhibits antitumoral effects in a breast cancer model

被引:48
作者
Yin, Tao [1 ,2 ]
He, Sisi [1 ,2 ]
Wang, Yongsheng [1 ,2 ,3 ,4 ]
机构
[1] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, West China Hosp, Ctr Canc, Chengdu 610041, Sichuan, Peoples R China
[3] Collaborat Innovat Ctr Biotherapy, Chengdu 610041, Sichuan, Peoples R China
[4] Sichuan Univ, West China Hosp, Dept Thorac Oncol, Ctr Canc, Chengdu 610041, Sichuan, Peoples R China
关键词
toll-like receptor 7; breast cancer; high mobility group box 1; angiogenesis; MOBILITY GROUP BOX-1; TUMOR REFRACTORINESS; MOLECULAR PATHWAYS; IMMUNE-RESPONSES; DRUG-RESISTANCE; DENDRITIC CELLS; MOUSE MODELS; TLR7; AGONIST; ANGIOGENESIS; THERAPY;
D O I
10.3892/mmr.2015.3885
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Toll-like receptors have been utilized in cancer therapeutic strategies in recent years. To the best of our knowledge, the systemic use of the toll-like receptor 7/8 (TLR7/8) agonist has not been investigated in a breast cancer model. In the current study, tumor growth following drug therapy was examined. Immunofluorescence and TUNEL staining were performed in order to examine the tumor vasculature and apoptosis, respectively. In addition, immunohistochemistry was used to assess HMGB1 in tumor tissues. Activated CD4(+) T cells in the peripheral blood were examined by flow cytometry. In the present study, it was identified that the TLR7/8 agonist, R848, exhibited a robust antitumoral effect. R848 reduced tumor vasculature and induced tumor cell apoptosis. In addition, R848 increased high mobility group box 1 expression in tumor tissues and activated CD4(+) T cells in the peripheral blood. A synergistic antitumoral effect of R848 and the anti-angiogenic agent, sunitinib, was observed. The present findings suggest that the TLR7/8 agonist may be a potential adjuvant to potentiate the effect of anti-angiogenic therapy.
引用
收藏
页码:3515 / 3520
页数:6
相关论文
共 33 条
  • [1] Topical TLR7 Agonist Imiquimod Can Induce Immune-Mediated Rejection of Skin Metastases in Patients with Breast Cancer
    Adams, Sylvia
    Kozhaya, Lina
    Martiniuk, Frank
    Meng, Tze-Chiang
    Chiriboga, Luis
    Liebes, Leonard
    Hochman, Tsivia
    Shuman, Nicholas
    Axelrod, Deborah
    Speyer, James
    Novik, Yelena
    Tiersten, Amy
    Goldberg, Judith D.
    Formenti, Silvia C.
    Bhardwaj, Nina
    Unutmaz, Derya
    Demaria, Sandra
    [J]. CLINICAL CANCER RESEARCH, 2012, 18 (24) : 6748 - 6757
  • [2] Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy
    Apetoh, Lionel
    Ghiringhelli, Francois
    Tesniere, Antoine
    Obeid, Michel
    Ortiz, Carla
    Criollo, Alfredo
    Mignot, Gregoire
    Maiuri, M. Chiara
    Ullrich, Evelyn
    Saulnier, Patrick
    Yang, Huan
    Amigorena, Sebastian
    Ryffel, Bernard
    Barrat, Franck J.
    Saftig, Paul
    Levi, Francis
    Lidereau, Rosette
    Nogues, Catherine
    Mira, Jean-Paul
    Chompret, Agnes
    Joulin, Virginie
    Clavel-Chapelon, Francoise
    Bourhis, Jean
    Andre, Fabrice
    Delaloge, Suzette
    Tursz, Thomas
    Kroemer, Guido
    Zitvogel, Laurence
    [J]. NATURE MEDICINE, 2007, 13 (09) : 1050 - 1059
  • [3] DAMPs, PAMPs and alarmins: all we need to know about danger
    Bianchi, Marco E.
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 2007, 81 (01) : 1 - 5
  • [4] Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors
    Casanovas, O
    Hicklin, DJ
    Bergers, G
    Hanahan, D
    [J]. CANCER CELL, 2005, 8 (04) : 299 - 309
  • [5] Reciprocal regulation by TLR4 and TGF-β in tumor-initiating stem-like cells
    Chen, Chia-Lin
    Tsukamoto, Hidekazu
    Liu, Jian-Chang
    Kashiwabara, Claudine
    Feldman, Douglas
    Sher, Linda
    Dooley, Steven
    French, Samuel W.
    Mishra, Lopa
    Petrovic, Lydia
    Jeong, Joseph H.
    Machida, Keigo
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (07) : 2832 - 2849
  • [6] An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy
    Chung, Alicia S.
    Wu, Xiumin
    Zhuang, Guanglei
    Ngu, Hai
    Kasman, Ian
    Zhang, Jianhuan
    Vernes, Jean-Michel
    Jiang, Zhaoshi
    Meng, Y. Gloria
    Peale, Franklin V.
    Ouyang, Wenjun
    Ferrara, Napoleone
    [J]. NATURE MEDICINE, 2013, 19 (09) : 1114 - 1123
  • [7] Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia
    Conley, Sarah J.
    Gheordunescu, Elizabeth
    Kakarala, Pramod
    Newman, Bryan
    Korkaya, Hasan
    Heath, Amber N.
    Clouthier, Shawn G.
    Wicha, Max S.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (08) : 2784 - 2789
  • [8] Synergy of Topical Toll-like Receptor 7 Agonist with Radiation and Low-Dose Cyclophosphamide in a Mouse Model of Cutaneous Breast Cancer
    Dewan, M. Zahidunnabi
    Vanpouille-Box, Claire
    Kawashima, Noriko
    DiNapoli, Sara
    Babb, James S.
    Formenti, Silvia C.
    Adams, Sylvia
    Demaria, Sandra
    [J]. CLINICAL CANCER RESEARCH, 2012, 18 (24) : 6668 - 6678
  • [9] Systemic delivery of a TLR7 agonist in combination with radiation primes durable antitumor immune responses in mouse models of lymphoma
    Dovedi, Simon J.
    Melis, Monique H. M.
    Wilkinson, Robert W.
    Adlard, Amy L.
    Stratford, Ian J.
    Honeychurch, Jamie
    Illidge, Timothy M.
    [J]. BLOOD, 2013, 121 (02) : 251 - 259
  • [10] Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products
    Dumitriu, IE
    Baruah, P
    Valentinis, B
    Voll, RE
    Herrmann, M
    Nawroth, PP
    Arnold, B
    Bianchi, ME
    Manfredi, AA
    Rovere-Querini, P
    [J]. JOURNAL OF IMMUNOLOGY, 2005, 174 (12) : 7506 - 7515