title: Suppression of T-cell expansion by melanoma is exerted on resting cells.
abstract: 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.
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Russ
authors.forename: Lucy
authors.initials: L
authors.lastname: Wentworth
authors.forename: Kyle
authors.initials: K
authors.lastname: Xu
authors.forename: Alexander
authors.initials: A
authors.lastname: Rakhmilevich
authors.forename: Christine M
authors.initials: CM
authors.lastname: Seroogy
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sondel
authors.forename: M
authors.initials: M
authors.lastname: Suresh
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm