TY - JOUR
T1 - Systemic GM-CSF recruits effector T cells into the tumor microenvironment in localized prostate cancer
AU - Wei, Xiao X.
AU - Chan, Stephen
AU - Kwek, Serena
AU - Lewis, Jera
AU - Dao, Vinh
AU - Zhang, Li
AU - Cooperberg, Matthew R.
AU - Ryan, Charles J.
AU - Lin, Amy M.
AU - Friedlander, Terence W.
AU - Rini, Brian
AU - Kane, Christopher
AU - Simko, Jeffry P.
AU - Carroll, Peter R.
AU - Small, Eric J.
AU - Fong, Lawrence
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/11
Y1 - 2016/11
N2 - 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.
AB - 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.
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U2 - 10.1158/2326-6066.CIR-16-0042
DO - 10.1158/2326-6066.CIR-16-0042
M3 - Article
C2 - 27688020
AN - SCOPUS:85016112467
SN - 2326-6066
VL - 4
SP - 948
EP - 958
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 11
ER -
