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.
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Acknowledgments
This work was supported by grant support from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Science Research and Development Service, Career Development Award (CDA-2), American College of Surgeons Faculty Research Fellowship, and Central Surgical Association Foundation Grant to CSC, and by support from NIH Grant AI48785 to MS.
Conflicts of interest
The authors declare they have no conflict of interest; the contents of this work do not represent the views of the Department of Veterans Affairs or the United States Government.
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Wentworth, L., Meyers, J.V., Alam, S. et al. Memory T cells are uniquely resistant to melanoma-induced suppression. Cancer Immunol Immunother 62, 149–159 (2013). https://doi.org/10.1007/s00262-012-1326-1
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DOI: https://doi.org/10.1007/s00262-012-1326-1