Cancer Immunology, Immunotherapy

, Volume 63, Issue 8, pp 859–867

B7-H1 signaling is integrated during CD8+ T cell priming and restrains effector differentiation

  • Rachel M. Gibbons
  • Xin Liu
  • Susan M. Harrington
  • Christopher J. Krco
  • Eugene D. Kwon
  • Haidong Dong
Original Article

DOI: 10.1007/s00262-014-1563-6

Cite this article as:
Gibbons, R.M., Liu, X., Harrington, S.M. et al. Cancer Immunol Immunother (2014) 63: 859. doi:10.1007/s00262-014-1563-6

Abstract

A promising strategy in tumor immunotherapy is the use of activated dendritic cells as vehicles for tumor vaccines with the goal of activating anti-tumor T cell responses. Current formulations for dendritic cell-based immunotherapies have limited effects on patient survival, providing motivation for further investigation of ways to enhance dendritic cell priming of anti-tumor T cell responses. Using a brief in vitro priming model, we have found that B7-H1 expressed by activated dendritic cells is integrated during priming of naïve CD8+ T cells and functions to limit the differentiation of effector T cell responses. CD8+ T cells primed by B7-H1-deficient dendritic cells exhibit increased production of IFN-γ, enhanced target cell killing, and improved anti-tumor activity. Additionally, enhanced memory populations arise from CD8+ T cells primed by B7-H1-deficient dendritic cells. Based on these findings, we suggest that early blockade of B7-H1 signaling should be investigated as a strategy to improve dendritic cell-based anti-tumor immunotherapy.

Keywords

T cell priming Co-stimulatory signaling Effector CD8+ T cells Memory CD8+ T cells 

Abbreviations

B6

C57BL6

BM

Bone marrow

CTL

Cytotoxic T lymphocyte

KO

Knock out

MFI

Mean fluorescence intensity

WT

Wild type

Supplementary material

262_2014_1563_MOESM1_ESM.pdf (503 kb)
Supplementary material 1 (PDF 502 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Rachel M. Gibbons
    • 1
  • Xin Liu
    • 2
  • Susan M. Harrington
    • 2
  • Christopher J. Krco
    • 2
  • Eugene D. Kwon
    • 2
    • 3
  • Haidong Dong
    • 2
    • 3
  1. 1.Biology DisciplineUniversity of MinnesotaMorrisUSA
  2. 2.Department of Urology, College of MedicineMayo ClinicRochesterUSA
  3. 3.Department of Immunology, College of MedicineMayo ClinicRochesterUSA

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