Mesenchymal stromal cells inhibit murine syngeneic anti-tumor immune responses by attenuating inflammation and reorganizing the tumor microenvironment

Jaime F. Modiano, Beth A. Lindborg, Ron T. McElmurry, Mitzi Lewellen, Colleen L. Forster, Edward A. Zamora, Jerome Schaack, Donald Bellgrau, Timothy D. O’Brien, Jakub Tolar

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The potential of mesenchymal stromal cells (MSCs) to inhibit anti-tumor immunity is becoming increasingly well recognized, but the precise steps affected by these cells during the development of an anti-tumor immune response remain incompletely understood. Here, we examined how MSCs affect the steps required to mount an effective anti-tumor immune response following administration of adenovirus Fas ligand (Ad-FasL) in the Lewis lung carcinoma (LL3) model. Administration of bone marrow-derived MSCs with LL3 cells accelerated tumor growth significantly. MSCs inhibited the inflammation induced by Ad-FasL in the primary tumors, precluding their rejection; MSCs also reduced the consequent expansion of tumor-specific T cells in the treated hosts. When immune T cells were transferred to adoptive recipients, MSCs impaired, but did not completely abrogate the ability of these T cells to promote elimination of secondary tumors. This impairment was associated with a modest reduction in tumor-infiltrating T cells, with a significant reduction in tumor-infiltrating macrophages, and with a reorganization of the stromal environment. Our data indicate that MSCs in the tumor environment reduce the efficacy of immunotherapy by creating a functional and anatomic barrier that impairs inflammation, T cell priming and expansion, and T cell function—including recruitment of effector cells.

Original languageEnglish (US)
Pages (from-to)1449-1460
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume64
Issue number11
DOIs
StatePublished - Nov 1 2015

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Tumor Microenvironment
Mesenchymal Stromal Cells
Inflammation
Neoplasms
T-Lymphocytes
Fas Ligand Protein
Adenoviridae
Lewis Lung Carcinoma
Immunotherapy
Immunity
Bone Marrow
Macrophages

Keywords

  • Animal model
  • Cancer
  • FasL
  • Mesenchymal stromal cells
  • Tumor immunotherapy

Cite this

Mesenchymal stromal cells inhibit murine syngeneic anti-tumor immune responses by attenuating inflammation and reorganizing the tumor microenvironment. / Modiano, Jaime F.; Lindborg, Beth A.; McElmurry, Ron T.; Lewellen, Mitzi; Forster, Colleen L.; Zamora, Edward A.; Schaack, Jerome; Bellgrau, Donald; O’Brien, Timothy D.; Tolar, Jakub.

In: Cancer Immunology, Immunotherapy, Vol. 64, No. 11, 01.11.2015, p. 1449-1460.

Research output: Contribution to journalArticle

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