Systemic GM-CSF recruits effector T cells into the tumor microenvironment in localized prostate cancer

Xiao X. Wei, Stephen Chan, Serena Kwek, Jera Lewis, Vinh Dao, Li Zhang, Matthew R. Cooperberg, Charles J. Ryan, Amy M. Lin, Terence W. Friedlander, Brian Rini, Christopher Kane, Jeffry P. Simko, Peter R. Carroll, Eric J. Small, Lawrence Fong

Research output: Contribution to journalArticle

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Abstract

Granulocytic-macrophage colony-stimulating factor (GMCSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients with localized prostate cancer undergoing radical prostatectomy. Patients received subcutaneous injections of GM-CSF (250 mg/m2/day) daily for 2 weeks (cohort 1; n = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6). Treatment was well tolerated with all grade 1 or 2 adverse events. Two patients had a decline in prostate-specific antigen (PSA) of more than 50%. GMCSF treatment increased the numbers of circulating mature myeloid dendritic cells, proliferating conventional CD4 T cells, proliferating CD8 T cells, and to a lesser magnitude FoxP3+ regulatory CD4 T cells. Although GM-CSF treatment did not augment antigen-presenting cell localization to the prostate, treatment was associated with recruitment of CD8+ T cells to the tumor. These results suggest that systemic GM-CSF can modulate T-cell infiltration in the tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)948-958
Number of pages11
JournalCancer Immunology Research
Volume4
Issue number11
DOIs
StatePublished - Nov 2016

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Tumor Microenvironment
Granulocyte-Macrophage Colony-Stimulating Factor
Prostatic Neoplasms
T-Lymphocytes
Macrophage Colony-Stimulating Factor
Cancer Vaccines
Antigen-Presenting Cells
Regulatory T-Lymphocytes
Myeloid Cells
Subcutaneous Injections
Therapeutics
Prostate-Specific Antigen
Prostatectomy
Immunotherapy
Dendritic Cells
Prostate
Neoplasms

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Systemic GM-CSF recruits effector T cells into the tumor microenvironment in localized prostate cancer. / Wei, Xiao X.; Chan, Stephen; Kwek, Serena; Lewis, Jera; Dao, Vinh; Zhang, Li; Cooperberg, Matthew R.; Ryan, Charles J.; Lin, Amy M.; Friedlander, Terence W.; Rini, Brian; Kane, Christopher; Simko, Jeffry P.; Carroll, Peter R.; Small, Eric J.; Fong, Lawrence.

In: Cancer Immunology Research, Vol. 4, No. 11, 11.2016, p. 948-958.

Research output: Contribution to journalArticle

Wei, XX, Chan, S, Kwek, S, Lewis, J, Dao, V, Zhang, L, Cooperberg, MR, Ryan, CJ, Lin, AM, Friedlander, TW, Rini, B, Kane, C, Simko, JP, Carroll, PR, Small, EJ & Fong, L 2016, 'Systemic GM-CSF recruits effector T cells into the tumor microenvironment in localized prostate cancer', Cancer Immunology Research, vol. 4, no. 11, pp. 948-958. https://doi.org/10.1158/2326-6066.CIR-16-0042
Wei, Xiao X. ; Chan, Stephen ; Kwek, Serena ; Lewis, Jera ; Dao, Vinh ; Zhang, Li ; Cooperberg, Matthew R. ; Ryan, Charles J. ; Lin, Amy M. ; Friedlander, Terence W. ; Rini, Brian ; Kane, Christopher ; Simko, Jeffry P. ; Carroll, Peter R. ; Small, Eric J. ; Fong, Lawrence. / Systemic GM-CSF recruits effector T cells into the tumor microenvironment in localized prostate cancer. In: Cancer Immunology Research. 2016 ; Vol. 4, No. 11. pp. 948-958.
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