Suppression of T-cell expansion by melanoma is exerted on resting cells

Andrew Russ, Lucy Wentworth, Kyle Xu, Alexander Rakhmilevich, Christine M. Seroogy, Paul M. Sondel, M. Suresh, Clifford S. Cho

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3848-3857
Number of pages10
JournalAnnals of Surgical Oncology
Volume18
Issue number13
DOIs
StatePublished - Dec 1 2011

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Melanoma
T-Lymphocytes
Lymphocytic choriomeningitis virus
Neoplasms
Cytotoxic T-Lymphocytes
Antigens
Adoptive Transfer
Virus Diseases
Tumor Burden
Inbred C57BL Mouse
Viruses
Growth
Population

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Russ, A., Wentworth, L., Xu, K., Rakhmilevich, A., Seroogy, C. M., Sondel, P. M., ... Cho, C. S. (2011). Suppression of T-cell expansion by melanoma is exerted on resting cells. Annals of Surgical Oncology, 18(13), 3848-3857. https://doi.org/10.1245/s10434-011-1667-6

Suppression of T-cell expansion by melanoma is exerted on resting cells. / Russ, Andrew; Wentworth, Lucy; Xu, Kyle; Rakhmilevich, Alexander; Seroogy, Christine M.; Sondel, Paul M.; Suresh, M.; Cho, Clifford S.

In: Annals of Surgical Oncology, Vol. 18, No. 13, 01.12.2011, p. 3848-3857.

Research output: Contribution to journalArticle

Russ, A, Wentworth, L, Xu, K, Rakhmilevich, A, Seroogy, CM, Sondel, PM, Suresh, M & Cho, CS 2011, 'Suppression of T-cell expansion by melanoma is exerted on resting cells', Annals of Surgical Oncology, vol. 18, no. 13, pp. 3848-3857. https://doi.org/10.1245/s10434-011-1667-6
Russ A, Wentworth L, Xu K, Rakhmilevich A, Seroogy CM, Sondel PM et al. Suppression of T-cell expansion by melanoma is exerted on resting cells. Annals of Surgical Oncology. 2011 Dec 1;18(13):3848-3857. https://doi.org/10.1245/s10434-011-1667-6
Russ, Andrew ; Wentworth, Lucy ; Xu, Kyle ; Rakhmilevich, Alexander ; Seroogy, Christine M. ; Sondel, Paul M. ; Suresh, M. ; Cho, Clifford S. / Suppression of T-cell expansion by melanoma is exerted on resting cells. In: Annals of Surgical Oncology. 2011 ; Vol. 18, No. 13. pp. 3848-3857.
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