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Melanoma-induced suppression of tumor antigen-specific T cell expansion is comparable to suppression of global T cell expansion
Authors:Russ Andrew J  Xu Kyle  Wentworth Lucy  Alam Sheeba  Meyers Justin V  Macklin Michael D  Rakhmilevich Alexander L  Rajamanickam Victoria  Suresh M  Cho Clifford S
Affiliation:aSection of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA;bWilliam S. Middleton Memorial VA Hospital, Madison, WI, USA;cUniversity of Wisconsin Comprehensive Cancer Center, Madison, WI, USA;dDepartment of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA;eDepartment of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI, USA
Abstract:We have observed that in vivo interaction between melanoma and resting T cells promotes suppression of antigen-driven proliferative T cell expansion. We hypothesized that this suppression would affect tumor antigen-specific T cell populations more potently than tumor-unrelated T cell populations. A B16F10 cell line was stably transfected to express low levels of the lymphocytic choriomeningitis virus (LCMV) glycoprotein GP33 (B16GP33). Mice bearing B16F10 or B16GP33 tumors were infected with LCMV, and proliferative expansion of LCMV epitope-specific T cell populations was quantified. In vitro and in vivo assays confirmed low levels of antigenic GP33 expression by B16GP33 tumors. Suppressed expansion of GP33-specific T cells was equivalent between mice bearing B16F10 and B16GP33 tumors. These observations suggest that the ability of growing melanoma tumors to impair antigen-driven proliferative expansion of activated T cells is global and not antigen-specific, and provide further insight into the influence of cancer on activated T cell homeostasis.
Keywords:T cell   Melanoma   Expansion   Antigen   LCMV
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