Systemic GM-CSF Recruits Effector T Cells into the Tumor Microenvironment in Localized Prostate Cancer.
Granulocytic-macrophage colony-stimulating factor (GM-CSF) 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 μg/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%. GM-CSF 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. Cancer Immunol Res; 4(11); 948-58. ©2016 AACR.
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Xiao X
XX
Wei
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Stephen
S
Chan
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Serena
S
Kwek
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Jera
J
Lewis
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Vinh
V
Dao
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Li
L
Zhang
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Matthew R
MR
Cooperberg
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Charles J
CJ
Ryan
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Amy M
AM
Lin
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Terence W
TW
Friedlander
Department of Hematology and Medical Oncology Cleveland, Clinic Taussig Cancer Institute, Cleveland, Ohio.
Brian
B
Rini
Department of Urology, University of California, San Diego, La Jolla, California.
Christopher
C
Kane
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Department of Anatomic Pathology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Jeffry P
JP
Simko
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Peter R
PR
Carroll
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.|Department of Urology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Eric J
EJ
Small
University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California. Lawrence.Fong@ucsf.edu.|Division of Hematology/Oncology, University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Lawrence
L
Fong
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
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