IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

Christopher J. Nirschl; Mayte Suárez-Fariñas; Benjamin Izar; Sanjay Prakadan; Ruth Dannenfelser; Itay Tirosh; Yong Liu; Qian Zhu; K. Sanjana P. Devi; Shaina L. Carroll; David Chau; Melika Rezaee; Tae Gyun Kim; Ruiqi Huang; Judilyn Fuentes-Duculan; George X. Song-Zhao; Nicholas Gulati; Michelle A. Lowes; Sandra L. King; Francisco J. Quintana; Young suk Lee; James G. Krueger; Kavita Y. Sarin; Charles H. Yoon; Levi Garraway; Aviv Regev; Alex K. Shalek; Olga Troyanskaya; Niroshana Anandasabapathy

doi:10.1016/j.cell.2017.06.016

IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

Christopher J. Nirschl, Mayte Suárez-Fariñas, Benjamin Izar, Sanjay Prakadan, Ruth Dannenfelser, Itay Tirosh, Yong Liu, Qian Zhu, K. Sanjana P. Devi, Shaina L. Carroll, David Chau, Melika Rezaee, Tae Gyun Kim, Ruiqi Huang, Judilyn Fuentes-Duculan, George X. Song-Zhao, Nicholas Gulati, Michelle A. Lowes, Sandra L. King, Francisco J. QuintanaYoung suk Lee, James G. Krueger, Kavita Y. Sarin, Charles H. Yoon, Levi Garraway, Aviv Regev, Alex K. Shalek, Olga Troyanskaya, Niroshana Anandasabapathy

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

Abstract

Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.

Original language	English
Pages (from-to)	127-141.e15
Journal	Cell
Volume	170
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2017.06.016
State	Published - 29 Jun 2017
Externally published	Yes

Keywords

IFNγ
dendritic cells
differentiation
homeostasis
immunotherapy
melanoma
suppressor-of-cytokine-signaling 2 (SOCS2)
tissue mononuclear phagocytes
tolerance
tumor microenvironment

All Science Journal Classification (ASJC) codes

General Biochemistry,Genetics and Molecular Biology

UN SDGs

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

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10.1016/j.cell.2017.06.016

Cite this

Nirschl, C. J., Suárez-Fariñas, M., Izar, B., Prakadan, S., Dannenfelser, R., Tirosh, I., Liu, Y., Zhu, Q., Devi, K. S. P., Carroll, S. L., Chau, D., Rezaee, M., Kim, T. G., Huang, R., Fuentes-Duculan, J., Song-Zhao, G. X., Gulati, N., Lowes, M. A., King, S. L., ... Anandasabapathy, N. (2017). IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment. Cell, 170(1), 127-141.e15. https://doi.org/10.1016/j.cell.2017.06.016

@article{b4b3eaa001c542f6b027204b0719d46a,

title = "IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment",

abstract = "Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.",

keywords = "IFNγ, dendritic cells, differentiation, homeostasis, immunotherapy, melanoma, suppressor-of-cytokine-signaling 2 (SOCS2), tissue mononuclear phagocytes, tolerance, tumor microenvironment",

author = "Nirschl, {Christopher J.} and Mayte Su{\'a}rez-Fari{\~n}as and Benjamin Izar and Sanjay Prakadan and Ruth Dannenfelser and Itay Tirosh and Yong Liu and Qian Zhu and Devi, {K. Sanjana P.} and Carroll, {Shaina L.} and David Chau and Melika Rezaee and Kim, {Tae Gyun} and Ruiqi Huang and Judilyn Fuentes-Duculan and Song-Zhao, {George X.} and Nicholas Gulati and Lowes, {Michelle A.} and King, {Sandra L.} and Quintana, {Francisco J.} and Lee, {Young suk} and Krueger, {James G.} and Sarin, {Kavita Y.} and Yoon, {Charles H.} and Levi Garraway and Aviv Regev and Shalek, {Alex K.} and Olga Troyanskaya and Niroshana Anandasabapathy",

note = "Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

year = "2017",

month = jun,

day = "29",

doi = "10.1016/j.cell.2017.06.016",

language = "الإنجليزيّة",

volume = "170",

pages = "127--141.e15",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "1",

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Nirschl, CJ, Suárez-Fariñas, M, Izar, B, Prakadan, S, Dannenfelser, R, Tirosh, I, Liu, Y, Zhu, Q, Devi, KSP, Carroll, SL, Chau, D, Rezaee, M, Kim, TG, Huang, R, Fuentes-Duculan, J, Song-Zhao, GX, Gulati, N, Lowes, MA, King, SL, Quintana, FJ, Lee, YS, Krueger, JG, Sarin, KY, Yoon, CH, Garraway, L, Regev, A, Shalek, AK, Troyanskaya, O & Anandasabapathy, N 2017, 'IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment', Cell, vol. 170, no. 1, pp. 127-141.e15. https://doi.org/10.1016/j.cell.2017.06.016

TY - JOUR

T1 - IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

AU - Nirschl, Christopher J.

AU - Suárez-Fariñas, Mayte

AU - Izar, Benjamin

AU - Prakadan, Sanjay

AU - Dannenfelser, Ruth

AU - Tirosh, Itay

AU - Liu, Yong

AU - Zhu, Qian

AU - Devi, K. Sanjana P.

AU - Carroll, Shaina L.

AU - Chau, David

AU - Rezaee, Melika

AU - Kim, Tae Gyun

AU - Huang, Ruiqi

AU - Fuentes-Duculan, Judilyn

AU - Song-Zhao, George X.

AU - Gulati, Nicholas

AU - Lowes, Michelle A.

AU - King, Sandra L.

AU - Quintana, Francisco J.

AU - Lee, Young suk

AU - Krueger, James G.

AU - Sarin, Kavita Y.

AU - Yoon, Charles H.

AU - Garraway, Levi

AU - Regev, Aviv

AU - Shalek, Alex K.

AU - Troyanskaya, Olga

AU - Anandasabapathy, Niroshana

PY - 2017/6/29

Y1 - 2017/6/29

N2 - Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.

AB - Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment.

KW - IFNγ

KW - dendritic cells

KW - differentiation

KW - homeostasis

KW - immunotherapy

KW - melanoma

KW - suppressor-of-cytokine-signaling 2 (SOCS2)

KW - tissue mononuclear phagocytes

KW - tolerance

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85021662906&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2017.06.016

DO - 10.1016/j.cell.2017.06.016

M3 - مقالة

C2 - 28666115

SN - 0092-8674

VL - 170

SP - 127-141.e15

JO - Cell

JF - Cell

IS - 1

ER -

IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

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