Cancer Immunology, Immunotherapy

, Volume 62, Issue 1, pp 149–159

Memory T cells are uniquely resistant to melanoma-induced suppression

  • Lucy Wentworth
  • Justin V. Meyers
  • Sheeba Alam
  • Andrew J. Russ
  • M. Suresh
  • Clifford S. Cho
Original Article

DOI: 10.1007/s00262-012-1326-1

Cite this article as:
Wentworth, L., Meyers, J.V., Alam, S. et al. Cancer Immunol Immunother (2013) 62: 149. doi:10.1007/s00262-012-1326-1

Abstract

We have previously observed that in vivo exposure to growing melanoma tumors fundamentally alters activated T cell homeostasis by suppressing the ability of naïve T cells to undergo antigen-driven proliferative expansion. We hypothesized that exposure of T cells in later stages of differentiation to melanoma would have similar suppressive consequences. C57BL/6 mice were inoculated with media or syngeneic B16F10 melanoma tumors 8 or 60 days after infection with lymphocytic choriomeningitis virus (LCMV), and splenic populations of LCMV-specific T cells were quantified using flow cytometry 18 days after tumor inoculation. Inoculation with melanoma on post-infection day 8 potentiated the contraction of previously activated T cells. This enhanced contraction was associated with increased apoptotic susceptibility among T cells from tumor-bearing mice. In contrast, inoculation with melanoma on post-infection day 60 did not affect the ability of previously established memory T cells to maintain themselves in stable numbers. In addition, the ability of previously established memory T cells to respond to LCMV challenge was unaffected by melanoma. Following adoptive transfer into melanoma-bearing mice, tumor-specific memory T cells were significantly more effective at controlling melanoma growth than equivalent numbers of tumor-specific effector T cells. These observations suggest that memory T cells are uniquely resistant to suppressive influences exerted by melanoma on activated T cell homeostasis; these findings may have implications for T cell–based cancer immunotherapy.

Keywords

Cancer T cell Melanoma LCMV Memory Immunotherapy 

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Lucy Wentworth
    • 1
    • 2
  • Justin V. Meyers
    • 1
  • Sheeba Alam
    • 1
  • Andrew J. Russ
    • 1
  • M. Suresh
    • 3
  • Clifford S. Cho
    • 1
    • 2
  1. 1.Section of Surgical OncologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Surgical ServiceWilliam S. Middleton Memorial VA HospitalMadisonUSA
  3. 3.Department of Pathobiological SciencesUniversity of Wisconsin School of Veterinary MedicineMadisonUSA