Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8+ T cells

被引:378
作者
Carretero, Rafael [1 ]
Sektioglu, Ibrahim M. [1 ]
Garbi, Natalio [1 ]
Salgado, Oscar C. [1 ]
Beckhove, Philipp [2 ,3 ,4 ]
Haemmerling, Guenter J. [1 ]
机构
[1] German Canc Res Ctr, Div Mol Immunol, Heidelberg, Germany
[2] German Canc Res Ctr, Div Translat Immunol, Heidelberg, Germany
[3] Univ Clin, Regensburg Ctr Intervent Immunol, Regensburg, Germany
[4] Univ Regensburg, D-93053 Regensburg, Germany
关键词
VASCULAR NORMALIZATION; MYELOID CELLS; IMMUNOTHERAPY; MICE; INTERLEUKIN-4; DISEASE; HEALTH; GROWTH; TUMORIGENESIS; INFLAMMATION;
D O I
10.1038/ni.3159
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tumor-associated eosinophilia is frequently observed in cancer. However, despite numerous studies of patients with cancer and mouse models of cancer, it has remained uncertain if eosinophils contribute to tumor immunity or are mere bystander cells. Here we report that activated eosinophils were essential for tumor rejection in the presence of tumor-specific CD8(+) T cells. Tumor-homing eosinophils secreted chemoattractants that guided T cells into the tumor, which resulted in tumor eradication and survival. Activated eosinophils initiated substantial changes in the tumor microenvironment, including macrophage polarization and normalization of the tumor vasculature, which are known to promote tumor rejection. Thus, our study presents a new concept for eosinophils in cancer that may lead to novel therapeutic strategies.
引用
收藏
页码:609 / +
页数:11
相关论文
共 47 条
  • [1] Pivotal advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response
    Cormier, Stephania A.
    Taranova, Anna G.
    Bedient, Carrie
    Nguyen, Thanh
    Protheroe, Cheryl
    Pero, Ralph
    Dimina, Dawn
    Ochkur, Sergei I.
    O'Neill, Katie
    Colbert, Dana
    Lombari, Theresa R.
    Constant, Stephanie
    McGarry, Michael P.
    Lee, James J.
    Lee, Nancy A.
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 2006, 79 (06) : 1131 - 1139
  • [2] MULTIPLE DEFECTS OF IMMUNE CELL-FUNCTION IN MICE WITH DISRUPTED INTERFERON-GAMMA GENES
    DALTON, DK
    PITTSMEEK, S
    KESHAV, S
    FIGARI, IS
    BRADLEY, A
    STEWART, TA
    [J]. SCIENCE, 1993, 259 (5102) : 1739 - 1742
  • [3] Eosinophils and Cancer
    Davis, Benjamin P.
    Rothenberg, Marc E.
    [J]. CANCER IMMUNOLOGY RESEARCH, 2014, 2 (01) : 1 - 8
  • [4] Experience in daily practice with ipilimumab for the treatment of patients with metastatic melanoma: an early increase in lymphocyte and eosinophil counts is associated with improved survival
    Delyon, J.
    Mateus, C.
    Lefeuvre, D.
    Lanoy, E.
    Zitvogel, L.
    Chaput, N.
    Roy, S.
    Eggermont, A. M. M.
    Routier, E.
    Robert, C.
    [J]. ANNALS OF ONCOLOGY, 2013, 24 (06) : 1697 - 1703
  • [5] Intratumoral Cytokines and Tumor Cell Biology Determine Spontaneous Breast Cancer-Specific Immune Responses and Their Correlation to Prognosis
    Domschke, Christoph
    Schuetz, Florian
    Ge, Yingzi
    Seibel, Tobias
    Falk, Christine
    Brors, Benedikt
    Vlodavsky, Israel
    Sommerfeldt, Nora
    Sinn, Hans-Peter
    Kuehnle, Marie-Christine
    Schneeweiss, Andreas
    Scharf, Alexander
    Sohn, Christof
    Schirrmacher, Volker
    Moldenhauer, Gerhard
    Momburg, Frank
    Beckhove, Philipp
    [J]. CANCER RESEARCH, 2009, 69 (21) : 8420 - 8428
  • [6] Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells
    Facciabene, Andrea
    Peng, Xiaohui
    Hagemann, Ian S.
    Balint, Klara
    Barchetti, Andrea
    Wang, Li-Ping
    Gimotty, Phyllis A.
    Gilks, C. Blake
    Lal, Priti
    Zhang, Lin
    Coukos, George
    [J]. NATURE, 2011, 475 (7355) : 226 - U141
  • [7] PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells
    Finlay, David K.
    Rosenzweig, Ella
    Sinclair, Linda V.
    Feijoo-Carnero, Carmen
    Hukelmann, Jens L.
    Rolf, Julia
    Panteleyev, Andrey A.
    Okkenhaug, Klaus
    Cantrell, Doreen A.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2012, 209 (13) : 2441 - 2453
  • [8] Prognostic and Predictive Impact of Intra- and Peritumoral Immune Infiltrates
    Fridman, Wolf Herman
    Galon, Jerome
    Pages, Franck
    Tartour, Eric
    Sautes-Fridman, Catherine
    Kroemer, Guido
    [J]. CANCER RESEARCH, 2011, 71 (17) : 5601 - 5605
  • [9] Coordinated regulation of myeloid cells by tumours
    Gabrilovich, Dmitry I.
    Ostrand-Rosenberg, Suzanne
    Bronte, Vincenzo
    [J]. NATURE REVIEWS IMMUNOLOGY, 2012, 12 (04) : 253 - 268
  • [10] Tumor associated macrophages and neutrophils in cancer
    Galdiero, Maria Rosaria
    Bonavita, Eduardo
    Barajon, Isabella
    Garlanda, Cecilia
    Mantovani, Alberto
    Jaillon, Sebastien
    [J]. IMMUNOBIOLOGY, 2013, 218 (11) : 1402 - 1410