title: Memory T cells are uniquely resistant to melanoma-induced suppression.
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.
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, Madison, WI 53792-7375, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Wentworth
authors.forename: Justin V
authors.initials: JV
authors.lastname: Meyers
authors.forename: Sheeba
authors.initials: S
authors.lastname: Alam
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Russ
authors.forename: M
authors.initials: M
authors.lastname: Suresh
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL