Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

O. Dmitrieva-Posocco; A. Dzutsev; D. F. Posocco; V. Hou; W. Yuan; V. Thovarai; I. A. Mufazalov; M. Gunzer; I. P. Shilovskiy; M. R. Khaitov; G. Trinchieri; A. Waisman; S. I. Grivennikov

doi:10.1016/j.immuni.2018.11.015

Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

O. Dmitrieva-Posocco, A. Dzutsev, D. F. Posocco, V. Hou, W. Yuan, V. Thovarai, I. A. Mufazalov, M. Gunzer, I. P. Shilovskiy, M. R. Khaitov, G. Trinchieri, A. Waisman, S. I. Grivennikov

Research output: Contribution to journal › Article › peer-review

127 Scopus citations

Abstract

Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression.

Original language	American English
Pages (from-to)	166-180 e7
Journal	Immunity
Volume	50
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2018.11.015
State	Published - 2019
Externally published	Yes

Keywords

Animals Carcinogenesis Cells, Cultured Colorectal Neoplasms/*immunology Humans Inflammation/*metabolism Interleukin-1/genetics/immunology/*metabolism Interleukin-17/*metabolism Interleukins/metabolism Mice Mice, Knockout Neutrophils/*immunology/ultrastructure Organ Specificity Receptors, Interleukin-1/genetics Salmonella/*immunology Salmonella Infections, Animal/*immunology Signal Transduction Tumor Microenvironment Interleukin-22 Cytokine Interleukin 1 cell type specific signaling colorectal cancer microbiota tumor elicited inflammation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.immuni.2018.11.015

https://www.ncbi.nlm.nih.gov/pubmed/30650375

Cite this

Dmitrieva-Posocco, O., Dzutsev, A., Posocco, D. F., Hou, V., Yuan, W., Thovarai, V., Mufazalov, I. A., Gunzer, M., Shilovskiy, I. P., Khaitov, M. R., Trinchieri, G., Waisman, A., & Grivennikov, S. I. (2019). Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer. Immunity, 50(1), 166-180 e7. https://doi.org/10.1016/j.immuni.2018.11.015

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title = "Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer",

abstract = "Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression.",

keywords = "Animals Carcinogenesis Cells, Cultured Colorectal Neoplasms/*immunology Humans Inflammation/*metabolism Interleukin-1/genetics/immunology/*metabolism Interleukin-17/*metabolism Interleukins/metabolism Mice Mice, Knockout Neutrophils/*immunology/ultrastructure Organ Specificity Receptors, Interleukin-1/genetics Salmonella/*immunology Salmonella Infections, Animal/*immunology Signal Transduction Tumor Microenvironment Interleukin-22 Cytokine Interleukin 1 cell type specific signaling colorectal cancer microbiota tumor elicited inflammation",

author = "O. Dmitrieva-Posocco and A. Dzutsev and Posocco, {D. F.} and V. Hou and W. Yuan and V. Thovarai and Mufazalov, {I. A.} and M. Gunzer and Shilovskiy, {I. P.} and Khaitov, {M. R.} and G. Trinchieri and A. Waisman and Grivennikov, {S. I.}",

note = "Dmitrieva-Posocco, Oxana Dzutsev, Amiran Posocco, David F Hou, Vivianty Yuan, Wuxing Thovarai, Vishal Mufazalov, Ilgiz A Gunzer, Matthias Shilovskiy, Igor P Khaitov, Musa R Trinchieri, Giorgio Waisman, Ari Grivennikov, Sergei I eng R00 DK088589/DK/NIDDK NIH HHS/ R01 CA227629/CA/NCI NIH HHS/ R01 CA218133/CA/NCI NIH HHS/ HHSN261200800001C/RC/CCR NIH HHS/ P30 CA006927/CA/NCI NIH HHS/ HHSN261200800001E/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2019/01/17 Immunity. 2019 Jan 15;50(1):166-180.e7. doi: 10.1016/j.immuni.2018.11.015.",

year = "2019",

doi = "10.1016/j.immuni.2018.11.015",

language = "American English",

volume = "50",

pages = "166--180 e7",

journal = "Immunity",

issn = "1097-4180",

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number = "1",

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Dmitrieva-Posocco, O, Dzutsev, A, Posocco, DF, Hou, V, Yuan, W, Thovarai, V, Mufazalov, IA, Gunzer, M, Shilovskiy, IP, Khaitov, MR, Trinchieri, G, Waisman, A & Grivennikov, SI 2019, 'Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer', Immunity, vol. 50, no. 1, pp. 166-180 e7. https://doi.org/10.1016/j.immuni.2018.11.015

TY - JOUR

T1 - Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

AU - Dmitrieva-Posocco, O.

AU - Dzutsev, A.

AU - Posocco, D. F.

AU - Hou, V.

AU - Yuan, W.

AU - Thovarai, V.

AU - Mufazalov, I. A.

AU - Gunzer, M.

AU - Shilovskiy, I. P.

AU - Khaitov, M. R.

AU - Trinchieri, G.

AU - Waisman, A.

AU - Grivennikov, S. I.

N1 - Dmitrieva-Posocco, Oxana Dzutsev, Amiran Posocco, David F Hou, Vivianty Yuan, Wuxing Thovarai, Vishal Mufazalov, Ilgiz A Gunzer, Matthias Shilovskiy, Igor P Khaitov, Musa R Trinchieri, Giorgio Waisman, Ari Grivennikov, Sergei I eng R00 DK088589/DK/NIDDK NIH HHS/ R01 CA227629/CA/NCI NIH HHS/ R01 CA218133/CA/NCI NIH HHS/ HHSN261200800001C/RC/CCR NIH HHS/ P30 CA006927/CA/NCI NIH HHS/ HHSN261200800001E/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2019/01/17 Immunity. 2019 Jan 15;50(1):166-180.e7. doi: 10.1016/j.immuni.2018.11.015.

PY - 2019

Y1 - 2019

N2 - Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression.

AB - Chronic inflammation drives the progression of colorectal cancer (CRC). Increased expression of interleukin (IL)-17A is associated with poor prognosis, and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway, in different cell types within the CRC microenvironment. Genetic deletion of the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in early tumor seed outgrowth. T cell specific ablation of IL-1R1 decreased tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in bacterial invasion into tumors, heightened inflammation and aggressive CRC progression. Thus, IL-1 signaling elicits cell-type-specific responses, which, in aggregate, set the inflammatory tone of the tumor microenvironment and determine the propensity for disease progression.

KW - Animals Carcinogenesis Cells, Cultured Colorectal Neoplasms/immunology Humans Inflammation/metabolism Interleukin-1/genetics/immunology/metabolism Interleukin-17/metabolism Interleukins/metabolism Mice Mice, Knockout Neutrophils/immunology/ultrastructure

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U2 - 10.1016/j.immuni.2018.11.015

DO - 10.1016/j.immuni.2018.11.015

M3 - Article

SN - 1097-4180

VL - 50

SP - 166-180 e7

JO - Immunity

JF - Immunity

IS - 1

ER -

Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

Abstract

Keywords

UN SDGs

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Cell-Type-Specific Responses to Interleukin-1 Control Microbial Invasion and Tumor-Elicited Inflammation in Colorectal Cancer

Abstract

Keywords

UN SDGs

Access to Document

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Cell Culture Facility

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