Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells

Mercedes B. Fuertes, Aalok K. Kacha, Justin Kline, Seng Ryong Woo, David M Kranz, Kenneth M. Murphy, Thomas F. Gajewski

Research output: Contribution to journalArticle

Abstract

Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c+ cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α+ dendritic cells, which were demonstrated to be essential using Batf3-/- mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α+ DCs.

Original languageEnglish (US)
Pages (from-to)2005-2016
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number10
DOIs
StatePublished - Sep 26 2011

Fingerprint

Interferon Type I
Dendritic Cells
T-Lymphocytes
Interferons
Neoplasms
Antigen-Presenting Cells
Melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells. / Fuertes, Mercedes B.; Kacha, Aalok K.; Kline, Justin; Woo, Seng Ryong; Kranz, David M; Murphy, Kenneth M.; Gajewski, Thomas F.

In: Journal of Experimental Medicine, Vol. 208, No. 10, 26.09.2011, p. 2005-2016.

Research output: Contribution to journalArticle

Fuertes, Mercedes B. ; Kacha, Aalok K. ; Kline, Justin ; Woo, Seng Ryong ; Kranz, David M ; Murphy, Kenneth M. ; Gajewski, Thomas F. / Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells. In: Journal of Experimental Medicine. 2011 ; Vol. 208, No. 10. pp. 2005-2016.
@article{24a51604c0cc4bd0934d5056d8635644,
title = "Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells",
abstract = "Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c+ cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α+ dendritic cells, which were demonstrated to be essential using Batf3-/- mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α+ DCs.",
author = "Fuertes, {Mercedes B.} and Kacha, {Aalok K.} and Justin Kline and Woo, {Seng Ryong} and Kranz, {David M} and Murphy, {Kenneth M.} and Gajewski, {Thomas F.}",
year = "2011",
month = "9",
day = "26",
doi = "10.1084/jem.20101159",
language = "English (US)",
volume = "208",
pages = "2005--2016",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "10",

}

TY - JOUR

T1 - Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8α+ dendritic cells

AU - Fuertes, Mercedes B.

AU - Kacha, Aalok K.

AU - Kline, Justin

AU - Woo, Seng Ryong

AU - Kranz, David M

AU - Murphy, Kenneth M.

AU - Gajewski, Thomas F.

PY - 2011/9/26

Y1 - 2011/9/26

N2 - Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c+ cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α+ dendritic cells, which were demonstrated to be essential using Batf3-/- mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α+ DCs.

AB - Despite lack of tumor control in many models, spontaneous T cell priming occurs frequently in response to a growing tumor. However, the innate immune mechanisms that promote natural antitumor T cell responses are undefined. In human metastatic melanoma, there was a correlation between a type I interferon (IFN) transcriptional profile and T cell markers in metastatic tumor tissue. In mice, IFN-β was produced by CD11c+ cells after tumor implantation, and tumor-induced T cell priming was defective in mice lacking IFN-α/βR or Stat1. IFN signaling was required in the hematopoietic compartment at the level of host antigen-presenting cells, and selectively for intratumoral accumulation of CD8α+ dendritic cells, which were demonstrated to be essential using Batf3-/- mice. Thus, host type I IFNs are critical for the innate immune recognition of a growing tumor through signaling on CD8α+ DCs.

UR - http://www.scopus.com/inward/record.url?scp=80355136945&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80355136945&partnerID=8YFLogxK

U2 - 10.1084/jem.20101159

DO - 10.1084/jem.20101159

M3 - Article

VL - 208

SP - 2005

EP - 2016

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 10

ER -