Low-Dose Irradiation Programs Macrophage Differentiation to an iNOS+/M1 Phenotype that Orchestrates Effective T Cell Immunotherapy

被引：1056

作者：

Klug, Felix ^{[1
,2
]}

Prakash, Hridayesh ^{[1
,2
,3
,5
]}

Huber, Peter E. ^{[6
,7
]}

Seibel, Tobias ^{[1
,2
]}

Bender, Noemi ^{[1
,2
]}

Halama, Niels ^{[8
]}

Pfirschke, Christina ^{[1
,2
]}

Voss, Ralf Holger ^{[9
]}

Timke, Carmen ^{[6
,7
]}

Urnansky, Ludmila ^{[1
,2
]}

Klapproth, Kay ^{[10
]}

Schaekel, Knut

Garbi, Natalio ^{[11
,12
,13
]}

Jaeger, Dirk ^{[8
]}

Weitz, Juergen ^{[4
]}

Schmitz-Winnenthal, Hubertus ^{[4
]}

Haemmerling, Guenter J. ^{[10
]}

Beckhove, Philipp ^{[1
,2
]}

机构：

[1] German Canc Res Ctr, Div Translat Immunol, D-69120 Heidelberg, Germany

[2] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany

[3] Heidelberg Univ, Med Ctr, Dept Dermatol, D-69120 Heidelberg, Germany

[4] Heidelberg Univ, Med Ctr, Dept Visceral Surg, D-69120 Heidelberg, Germany

[5] Univ Hyderabad, Sch Life Sci, Dept Biochem, Hyderabad 500046, Andhra Pradesh, India

[6] DKFZ, Dept Mol & Radiat Oncol, D-69120 Heidelberg, Germany

[7] Heidelberg Univ, Med Ctr, D-69120 Heidelberg, Germany

[8] Heidelberg Univ, Med Ctr, NCT, Dept Med Oncol, D-69120 Heidelberg, Germany

[9] Univ Hosp Mainz, Dept Hematol, D-55131 Mainz, Germany

[10] DKFZ, Div Cellular Immunol, D-69120 Heidelberg, Germany

[11] DKFZ, Div Mol Immunol, D-69120 Heidelberg, Germany

[12] Univ Bonn, Inst Mol Med, D-53113 Bonn, Germany

[13] Univ Bonn, Inst Expt Immunol, D-53113 Bonn, Germany

来源：

CANCER CELL | 2013年 / 24卷 / 05期

关键词：

TUMOR-ASSOCIATED MACROPHAGES; PANCREATIC-CANCER; BONE-MARROW; INFLAMMATION; ENDOTHELIUM; MICROENVIRONMENT; TUMORIGENESIS; INFILTRATION; ANGIOGENESIS; DESTRUCTION;

D O I：

10.1016/j.ccr.2013.09.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Inefficient T cell migration is a major limitation of cancer immunotherapy. Targeted activation of the tumor microenvironment may overcome this barrier. We demonstrate that neoadjuvant local low-dose gamma irradiation (LDI) causes normalization of aberrant vasculature and efficient recruitment of tumor-specific T cells in human pancreatic carcinomas and T-cell-mediated tumor rejection and prolonged survival in otherwise immune refractory spontaneous and xenotransplant mouse tumor models. LDI (local or pre-adoptive-transfer) programs the differentiation of iNOS(+) M1 macrophages that orchestrate CTL recruitment into and killing within solid tumors through iNOS by inducing endothelial activation and the expression of TH1 chemokines and by suppressing the production of angiogenic, imnnunosuppressive, and tumor growth factors.

引用

页码：589 / 602

页数：14

共 37 条

[1]

Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment [J].

Allavena, P. ;

Mantovani, A. .

CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2012, 167 (02) :195-205

[2]

Current developments of immunotherapy in the clinic [J].

Antonia, S ;

Mulé, JJ ;

Weber, JS .

CURRENT OPINION IN IMMUNOLOGY, 2004, 16 (02) :130-136

[3]

Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer [J].

Bayne, Lauren J. ;

Beatty, Gregory L. ;

Jhala, Nirag ;

Clark, Carolyn E. ;

Rhim, Andrew D. ;

Stanger, Ben Z. ;

Vonderheide, Robert H. .

CANCER CELL, 2012, 21 (06) :822-835

[4]

Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancer [J].

Cao, ZA ;

Daniel, D ;

Hanahan, D .

BMC CANCER, 2002, 2 (1)

[5]

Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer [J].

De Monte, Lucia ;

Reni, Michele ;

Tassi, Elena ;

Clavenna, Daniela ;

Papa, Ilenia ;

Recalde, Helios ;

Braga, Marco ;

Di Carlo, Valerio ;

Doglioni, Claudio ;

Protti, Maria Pia .

JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (03) :469-478

[6]

Intratumoral Cytokines and Tumor Cell Biology Determine Spontaneous Breast Cancer-Specific Immune Responses and Their Correlation to Prognosis [J].

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 .

CANCER RESEARCH, 2009, 69 (21) :8420-8428

[7]

Bone marrow as a priming site for T-cell responses to blood-borne antigen [J].

Feuerer, M ;

Beckhove, P ;

Garbi, N ;

Mahnke, Y ;

Limmer, A ;

Hommel, M ;

Hämmerling, GJ ;

Kyewski, B ;

Hamann, A ;

Umansky, V ;

Schirrmacher, V .

NATURE MEDICINE, 2003, 9 (09) :1151-1157

[8]

Prognostic and Predictive Impact of Intra- and Peritumoral Immune Infiltrates [J].

Fridman, Wolf Herman ;

Galon, Jerome ;

Pages, Franck ;

Tartour, Eric ;

Sautes-Fridman, Catherine ;

Kroemer, Guido .

CANCER RESEARCH, 2011, 71 (17) :5601-5605

[9]

Myeloid-derived suppressor cells as regulators of the immune system [J].

Gabrilovich, Dmitry I. ;

Nagaraj, Srinivas .

NATURE REVIEWS IMMUNOLOGY, 2009, 9 (03) :162-174

[10]

Ganss R, 1998, CANCER RES, V58, P4673

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