CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages

David G. DeNardo, Jairo B. Barreto, Pauline Andreu, Lesley Vasquez, David Tawfik, Nikita Kolhatkar, Lisa Coussens

Research output: Contribution to journalArticle

727 Citations (Scopus)

Abstract

During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we demonstrate that IL-4-expressing CD4+ T lymphocytes indirectly promote invasion and subsequent metastasis of mammary adenocarcinomas by directly regulating the phenotype and effector function of tumor-associated CD11b+Gr1-F4/80+ macrophages that in turn enhance metastasis through activation of epidermal growth factor receptor signaling in malignant mammary epithelial cells. Together, these data indicate that antitumor acquired immune programs can be usurped in protumor microenvironments and instead promote malignancy by engaging cellular components of the innate immune system functionally involved in regulating epithelial cell behavior.

Original languageEnglish (US)
Pages (from-to)91-102
Number of pages12
JournalCancer Cell
Volume16
Issue number2
DOIs
StatePublished - Aug 4 2009
Externally publishedYes

Fingerprint

Breast
Macrophages
Breast Neoplasms
Neoplasm Metastasis
T-Lymphocytes
Lung
Leukocytes
Epithelial Cells
Epidermal Growth Factor Receptor
Interleukin-4
Disease Progression
Immune System
Immunity
Neoplasms
Carcinogenesis
Adenocarcinoma
Phenotype

Keywords

  • CELLCYCLE
  • CELLIMMUNO

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages. / DeNardo, David G.; Barreto, Jairo B.; Andreu, Pauline; Vasquez, Lesley; Tawfik, David; Kolhatkar, Nikita; Coussens, Lisa.

In: Cancer Cell, Vol. 16, No. 2, 04.08.2009, p. 91-102.

Research output: Contribution to journalArticle

DeNardo, David G. ; Barreto, Jairo B. ; Andreu, Pauline ; Vasquez, Lesley ; Tawfik, David ; Kolhatkar, Nikita ; Coussens, Lisa. / CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages. In: Cancer Cell. 2009 ; Vol. 16, No. 2. pp. 91-102.
@article{07834cd0943c45838b68a447913a9e5e,
title = "CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages",
abstract = "During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we demonstrate that IL-4-expressing CD4+ T lymphocytes indirectly promote invasion and subsequent metastasis of mammary adenocarcinomas by directly regulating the phenotype and effector function of tumor-associated CD11b+Gr1-F4/80+ macrophages that in turn enhance metastasis through activation of epidermal growth factor receptor signaling in malignant mammary epithelial cells. Together, these data indicate that antitumor acquired immune programs can be usurped in protumor microenvironments and instead promote malignancy by engaging cellular components of the innate immune system functionally involved in regulating epithelial cell behavior.",
keywords = "CELLCYCLE, CELLIMMUNO",
author = "DeNardo, {David G.} and Barreto, {Jairo B.} and Pauline Andreu and Lesley Vasquez and David Tawfik and Nikita Kolhatkar and Lisa Coussens",
year = "2009",
month = "8",
day = "4",
doi = "10.1016/j.ccr.2009.06.018",
language = "English (US)",
volume = "16",
pages = "91--102",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - CD4+ T Cells Regulate Pulmonary Metastasis of Mammary Carcinomas by Enhancing Protumor Properties of Macrophages

AU - DeNardo, David G.

AU - Barreto, Jairo B.

AU - Andreu, Pauline

AU - Vasquez, Lesley

AU - Tawfik, David

AU - Kolhatkar, Nikita

AU - Coussens, Lisa

PY - 2009/8/4

Y1 - 2009/8/4

N2 - During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we demonstrate that IL-4-expressing CD4+ T lymphocytes indirectly promote invasion and subsequent metastasis of mammary adenocarcinomas by directly regulating the phenotype and effector function of tumor-associated CD11b+Gr1-F4/80+ macrophages that in turn enhance metastasis through activation of epidermal growth factor receptor signaling in malignant mammary epithelial cells. Together, these data indicate that antitumor acquired immune programs can be usurped in protumor microenvironments and instead promote malignancy by engaging cellular components of the innate immune system functionally involved in regulating epithelial cell behavior.

AB - During breast cancer development, increased presence of leukocytes in neoplastic stroma parallels disease progression; however, the functional significance of leukocytes in regulating protumor versus antitumor immunity in the breast remains poorly understood. Utilizing the MMTV-PyMT model of mammary carcinogenesis, we demonstrate that IL-4-expressing CD4+ T lymphocytes indirectly promote invasion and subsequent metastasis of mammary adenocarcinomas by directly regulating the phenotype and effector function of tumor-associated CD11b+Gr1-F4/80+ macrophages that in turn enhance metastasis through activation of epidermal growth factor receptor signaling in malignant mammary epithelial cells. Together, these data indicate that antitumor acquired immune programs can be usurped in protumor microenvironments and instead promote malignancy by engaging cellular components of the innate immune system functionally involved in regulating epithelial cell behavior.

KW - CELLCYCLE

KW - CELLIMMUNO

UR - http://www.scopus.com/inward/record.url?scp=67651160649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67651160649&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2009.06.018

DO - 10.1016/j.ccr.2009.06.018

M3 - Article

C2 - 19647220

AN - SCOPUS:67651160649

VL - 16

SP - 91

EP - 102

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -