caa a22 4500 445338563 CHVBK 20180317142804.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1245/s10434-011-1667-6 doi (NATIONALLICENCE)springer-10.1245/s10434-011-1667-6 Suppression of T-Cell Expansion by Melanoma is Exerted on Resting Cells [Elektronische Daten] [Andrew Russ, Lucy Wentworth, Kyle Xu, Alexander Rakhmilevich, Christine Seroogy, Paul Sondel, M. Suresh, Clifford Cho] Background: Immunotherapeutic cancer protocols often rely on the ability to promote proliferative expansion of tumor-specific T-cell, but the influence of cancer on in vivo T-cell expansion remains largely undefined. Methods: The ability of control and B16F10 melanoma-bearing C57BL/6 mice to expand lymphocytic choriomeningitis virus antigen-specific T-cell populations in response to acute viral infection was compared by using flow cytometric assays of splenocytes. Results: The ability to expand virus-specific CD8+ and CD4+ T-cells was globally and markedly suppressed in tumor-bearing mice. Expanded cytotoxic T lymphocytes (CTLs) retained in vivo and in vitro functionality, suggesting that melanoma growth did not induce T-cell anergy. The magnitude of suppressed proliferative expansion was proportional to the extent of tumor burden. Melanoma-induced suppression of CTL expansion was correlated with upregulated apoptotic activity and hampered the induction of memory precursor effector cells. Adoptive transfer of resting LCMV antigen-specific T-cells before or after tumor establishment demonstrated that a critical period of in vivo exposure of resting T-cells to growing melanoma was responsible for the induction of suppressed expansion. This suppression was durable; surgical resection of melanoma after in vivo exposure to resting T-cells but before antigenic stimulation did not restore full expansion. Conclusions: These data suggest that growing melanoma tumors exert a global, antigen-independent influence on resting T-cells that fundamentally reprograms their ability to undergo proliferative expansion in response to subsequent antigenic stimulation. This finding may have direct implications for T-cell-based immunotherapeutic strategies. Society of Surgical Oncology, 2011 Russ Andrew Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut Wentworth Lucy Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut Xu Kyle Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut Rakhmilevich Alexander Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut Seroogy Christine Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut Sondel Paul Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut Suresh M. Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI, USA aut Cho Clifford Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut Annals of Surgical Oncology Springer-Verlag 18/13(2011-12-01), 3848-3857 1068-9265 18:13<3848 2011 18 10434 https://doi.org/10.1245/s10434-011-1667-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1245/s10434-011-1667-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Russ Andrew Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut NATIONALLICENCE 700 1- Wentworth Lucy Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut NATIONALLICENCE 700 1- Xu Kyle Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut NATIONALLICENCE 700 1- Rakhmilevich Alexander Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut NATIONALLICENCE 700 1- Seroogy Christine Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut NATIONALLICENCE 700 1- Sondel Paul Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut NATIONALLICENCE 700 1- Suresh M. Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI, USA aut NATIONALLICENCE 700 1- Cho Clifford Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA aut NATIONALLICENCE 773 0- Annals of Surgical Oncology Springer-Verlag 18/13(2011-12-01), 3848-3857 1068-9265 18:13<3848 2011 18 10434 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer