Dataciencia

Colección SciELO Chile

Interleukin-17-induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer

Indexado

WoS	WOS:000599858600010
Scopus	SCOPUS_ID:85090170903

DOI

10.1084/JEM.20190354

Año

2020

Tipo

artículo de investigación

Citas Totales

Autores Afiliación Chile

Instituciones Chile

% Participación
Internacional

Autores
Afiliación Extranjera

Instituciones
Extranjeras

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with an immunosuppressive microenvironment that is resistant to most therapies. IL17 is involved in pancreatic tumorigenesis, but its role in invasive PDAC is undetermined. We hypothesized that IL17 triggers and sustains PDAC immunosuppression. We inhibited IL17/IL17RA signaling using pharmacological and genetic strategies alongside mass cytometry and multiplex immunofluorescence techniques. We uncovered that IL17 recruits neutrophils, triggers neutrophil extracellular traps (NETs), and excludes cytotoxic CD8 T cells from tumors. Additionally, IL17 blockade increases immune checkpoint blockade (PD-1, CTLA4) sensitivity. Inhibition of neutrophils or Padi4-dependent NETosis phenocopies IL17 neutralization. NMR spectroscopy revealed changes in tumor lactate as a potential early biomarker for IL17/PD-1 combination efficacy. Higher expression of IL17 and PADI4 in human PDAC corresponds with poorer prognosis, and the serum of patients with PDAC has higher potential for NETosis. Clinical studies with IL17 and checkpoint blockade represent a novel combinatorial therapy with potential efficacy for this lethal disease.

Revista

Revista	ISSN
Journal Of Experimental Medicine	0022-1007

Métricas Externas

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Disciplinas de Investigación

WOS
Immunology
Medicine, Research & Experimental

Scopus
Immunology And Allergy
Immunology

SciELO
Sin Disciplinas

Muestra la distribución de disciplinas para esta publicación.

Publicaciones WoS (Ediciones: ISSHP, ISTP, AHCI, SSCI, SCI), Scopus, SciELO Chile.

Colaboración Institucional

Muestra la distribución de colaboración, tanto nacional como extranjera, generada en esta publicación.

Autores - Afiliación

Ord.	Autor	Género	Institución - País
1	Zhang, Yu	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
2	Chandra, Vidhi	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
3	Sanchez, Erick Riquelme	Hombre	University of Texas Health Science Center at Houston - Estados Unidos Universidad Mayor - Chile University of Texas System - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos
3	Riquelme Sanchez, Erick	Hombre	University of Texas MD Anderson Cancer Center - Estados Unidos Universidad Mayor - Chile Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos
4	Dutta, Prasanta	Mujer	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
5	Quesada, Pompeyo R.	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
6	Rakoski, Amanda	Mujer	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
7	Zoltan, Michelle	Mujer	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
8	Arora, Nivedita	-	University of Minnesota Twin Cities - Estados Unidos Univ Minnesota - Estados Unidos
9	Baydogan, Seyda	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
10	Horne, William	Hombre	University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh - Estados Unidos Childrens Hosp Pittsburgh - Estados Unidos UPMC Children’s Hospital of Pittsburgh - Estados Unidos
11	Burks, Jared	Hombre	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
12	Xu, Hanwen	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
13	Hussain, Perwez	-	National Cancer Institute (NCI) - Estados Unidos NCI - Estados Unidos
14	Wang, Huamin	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
15	Gupta, Sonal	Mujer	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
16	Maitra, Anirban	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
17	Bailey, Jennifer M.	Mujer	University of Texas Health Science Center at Houston - Estados Unidos University of Texas System - Estados Unidos Univ Texas Hlth Sci Ctr Houston - Estados Unidos McGovern Medical School - Estados Unidos
18	Moghaddam, Seyed J.	Hombre	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
19	Banerjee, Sulagna	-	Sylvester Comprehensive Cancer Center - Estados Unidos Univ Miami Hlth Syst - Estados Unidos
20	Sahin, Ismet	Hombre	Texas Southern University - Estados Unidos Texas Southern Univ - Estados Unidos
21	Bhattacharya, Pratip	-	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos
22	McAllister, Florencia	Mujer	University of Texas MD Anderson Cancer Center - Estados Unidos University of Texas Health Science Center at Houston - Estados Unidos Univ Texas MD Anderson Canc Ctr - Estados Unidos University of Texas System - Estados Unidos

Muestra la afiliación y género (detectado) para los co-autores de la publicación.

Financiamiento

Fuente
National Cancer Institute
University of Texas MD Anderson Cancer Center
V Foundation for Cancer Research
Andrew Sabin Family Foundation
National Pancreas Foundation
Pancreatic Cancer Action Network
AGA Research Foundation
Paul Calabresi K12 (National Cancer Institute)
Stand Up to Cancer/American Association for Cancer Research Interception Team
Pancreatic Cancer Action Network/American Association for Cancer Research career development award
Pancreatic Cancer Action Network/American Association for Cancer Research

Muestra la fuente de financiamiento declarada en la publicación.

Agradecimientos

Agradecimiento
F. McAllister received support from a Pancreatic Cancer Action Network/American Association for Cancer Research career development award (14-20-25 MCAL), the National Pancreas Foundation, the V Foundation for Cancer Research (translational award), Paul Calabresi K12 (National Cancer Institute grant K12CA088084-16A1 awarded to The University of Texas MD Anderson Cancer Center), the Andrew Sabin Family Foundation, the Stand Up to Cancer/American Association for Cancer Research Interception Team, and philanthropic funds from The University of Texas MD Anderson Cancer Center and the AGA Research Foundation.
F. McAllister received support from a Pancreatic Cancer Action Network/American Association for Cancer Research career development award (14-20-25 MCAL), the National Pancreas Foundation, the V Foundation for Cancer Research (translational award), Paul Calabresi K12 (National Cancer Institute grant K12CA088084-16A1 awarded to The University of Texas MD Anderson Cancer Center), the Andrew Sabin Family Foundation, the Stand Up to Cancer/American Association for Cancer Research Interception Team, and philanthropic funds from The University of Texas MD Anderson Cancer Center and the AGA Research Foundation.

Agradecimiento

F. McAllister received support from a Pancreatic Cancer Action Network/American Association for Cancer Research career development award (14-20-25 MCAL), the National Pancreas Foundation, the V Foundation for Cancer Research (translational award), Paul Calabresi K12 (National Cancer Institute grant K12CA088084-16A1 awarded to The University of Texas MD Anderson Cancer Center), the Andrew Sabin Family Foundation, the Stand Up to Cancer/American Association for Cancer Research Interception Team, and philanthropic funds from The University of Texas MD Anderson Cancer Center and the AGA Research Foundation.