Neutrophils and Snail Orchestrate the Establishment of a Pro-tumor Microenvironment in Lung Cancer

被引：169

作者：

Faget, Julien ^{[1
]}

Groeneveld, Svenja ^{[1
]}

Boivin, Gael ^{[2
]}

Sankar, Martial ^{[3
]}

Zangger, Nadine ^{[1
,4
]}

Garcia, Miguel ^{[5
]}

Guex, Nicolas ^{[3
]}

Zlobec, Inti ^{[6
]}

Steiner, Loic ^{[1
]}

Piersigilli, Alessandra ^{[7
,8
]}

Xenarios, Ioannis ^{[3
]}

Meylan, Etienne ^{[1
]}

机构：

[1] Ecole Polytech Fed Lausanne, Sch Life Sci, Swiss Inst Expt Canc Res, CH-1015 Lausanne, Switzerland

[2] Univ Lausanne, Ctr Hosp Univ Vaudois, Dept Oncol, Radiobiol Lab, CH-1011 Lausanne, Switzerland

[3] SIB Swiss Inst Bioinformat, Vital IT, CH-1015 Lausanne, Switzerland

[4] SIB, Bioinformat Core Facil, CH-1015 Lausanne, Switzerland

[5] Ecole Polytech Fed Lausanne, Sch Life Sci, Flow Cytometry Core Facil, CH-1015 Lausanne, Switzerland

[6] Univ Bern, Inst Pathol, CH-3008 Bern, Switzerland

[7] Univ Bern, Inst Anim Pathol, CH-3012 Bern, Switzerland

[8] Ecole Polytech Fed Lausanne, Sch Life Sci, CH-1015 Lausanne, Switzerland

来源：

CELL REPORTS | 2017年 / 21卷 / 11期

基金：

瑞士国家科学基金会;

关键词：

TERTIARY LYMPHOID STRUCTURES; FAS LIGAND EXPRESSION; T-CELL RESPONSES; CHECKPOINT BLOCKADE; IMMUNE PRIVILEGE; METASTASIS; ADENOCARCINOMA; CHEMOTHERAPY; PROGRESSION; MECHANISM;

D O I：

10.1016/j.celrep.2017.11.052

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1 + neutrophils to disease progression. Depletion experiments showed that Gr1 + cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful antiPD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration. Cxcl2 was produced mainly by neutrophils themselves in response to a factor secreted by Snail-expressing tumor cells. We therefore propose a vicious cycle encompassing neutrophils and Snail to maintain a deleterious tumor microenvironment.

引用

页码：3190 / 3204

页数：15

共 36 条

[1] EMT: 2016 [J].

Angela Nieto, M. ;

Huang, Ruby Yun-Ju ;

Jackson, Rebecca A. ;

Thiery, Jean Paul .

CELL, 2016, 166 (01) :21-45

[2] IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis [J].

Coffelt, Seth B. ;

Kersten, Kelly ;

Doornebal, Chris W. ;

Weiden, Jorieke ;

Vrijland, Kim ;

Hau, Cheei-Sing ;

Verstegen, Niels J. M. ;

Ciampricotti, Metamia ;

Hawinkels, Lukas J. A. C. ;

Jonkers, Jos ;

de Visser, Karin E. .

NATURE, 2015, 522 (7556) :345-+

[3] Tertiary lymphoid structures in cancer and beyond [J].

Dieu-Nosjean, Marie-Caroline ;

Goc, Jeremy ;

Giraldo, Nicolas A. ;

Sautes-Fridman, Catherine ;

Fridman, Wolf Herman .

TRENDS IN IMMUNOLOGY, 2014, 35 (11) :571-580

[4] Endogenous T Cell Responses to Antigens Expressed in Lung Adenocarcinomas Delay Malignant Tumor Progression [J].

DuPage, Michel ;

Cheung, Ann F. ;

Mazumdar, Claire ;

Winslow, Monte M. ;

Bronson, Roderick ;

Schmidt, Leah M. ;

Crowley, Denise ;

Chen, Jianzhu ;

Jacks, Tyler .

CANCER CELL, 2011, 19 (01) :72-85

[5] Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 [J].

Ferlay, Jacques ;

Soerjomataram, Isabelle ;

Dikshit, Rajesh ;

Eser, Sultan ;

Mathers, Colin ;

Rebelo, Marise ;

Parkin, Donald Maxwell ;

Forman, David ;

Bray, Freddie .

INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) :E359-E386

[6] Type, density, and location of immune cells within human colorectal tumors predict clinical outcome [J].

Galon, Jerom ;

Costes, Anne ;

Sanchez-Cabo, Fatima ;

Kirilovsky, Amos ;

Mlecnik, Bernhard ;

Lagorce-Pages, Christine ;

Tosolini, Marie ;

Camus, Matthieu ;

Berger, Anne ;

Wind, Philippe ;

Zinzindohoue, Franck ;

Bruneval, Patrick ;

Cugnenc, Paul-Henri ;

Trajanoski, Zlatko ;

Fridman, Wolf-Herman ;

Pages, Franck .

SCIENCE, 2006, 313 (5795) :1960-1964

[7] Characteristics of tertiary lymphoid structures in primary cancers [J].

Goc, Jeremy ;

Fridman, Wolf-Herman ;

Sautes-Fridman, Catherine ;

Dieu-Nosjean, Marie-Caroline .

ONCOIMMUNOLOGY, 2013, 2 (12) :1-9

[8] Acetylation of Snail Modulates the Cytokinome of Cancer Cells to Enhance the Recruitment of Macrophages [J].

Hsu, Dennis Shin-Shian ;

Wang, Hsiao-Jung ;

Tai, Shyh-Kuan ;

Chou, Chun-Hung ;

Hsieh, Chia-Hsin ;

Chiu, Po-Hsien ;

Chen, Nien-Jung ;

Yang, Muh-Hwa .

CANCER CELL, 2014, 26 (04) :534-548

[9] Prognostic significance of hypoxia-inducible factor-1α, TWIST1 and Snail expression in resectable non-small cell lung cancer [J].

Hung, J-J ;

Yang, M-H ;

Hsu, H-S ;

Hsu, W-H ;

Liu, J-S ;

Wu, K-J .

THORAX, 2009, 64 (12) :1082-1089

[10] Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer Progression and Resistance to Chemotherapy [J].

Incio, Joao ;

Liu, Hao ;

Suboj, Priya ;

Chin, Shan M. ;

Chen, Ivy X. ;

Pinter, Matthias ;

Ng, Mei R. ;

Nia, Hadi T. ;

Grahovac, Jelena ;

Kao, Shannon ;

Babykutty, Suboj ;

Huang, Yuhui ;

Jung, Keehoon ;

Rahbari, Nuh N. ;

Han, Xiaoxing ;

Chauhan, Vikash P. ;

Martin, John D. ;

Kahn, Julia ;

Huang, Peigen ;

Desphande, Vikram ;

Michaelson, James ;

Michelakos, Theodoros P. ;

Ferrone, Cristina R. ;

Soares, Raquel ;

Boucher, Yves ;

Fukumura, Dai ;

Jain, Rakesh K. .

CANCER DISCOVERY, 2016, 6 (08) :852-869

← 1 2 3 4 →