Abstract
Abstract Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) is a bone marrow growth factor that is often used as an adjuvant in cancer vaccine clinical trials and has the potential to enhance antitumor efficacy in combination with immune checkpoint blockade in preclinical studies and clinical trials. The effect of GM-CSF remains controversial, however. In this study, we sought to characterize the systemic and tissue-specific effects of GM-CSF in prostate cancer patients in the preoperative setting. Methods: Patients with localized prostate cancer were treated on an open-label phase I/II study of neoadjuvant GM-CSF prior to planned radical prostatectomy (NCT00305669). Patients received GM-CSF 250mcg/m2 subcutaneously on days 1-14 (cohort 1), days1-21 (cohort 2), or days 1-28 (cohort 3), and underwent radical prostatectomy (RP) within 5 days after the last dose of GM-CSF. Blood collected at baseline, day 14, pre-RP, and 6 weeks post-RP were analyzed for immune cell subsets by flow cytometry. Immune infiltration in RP tissue were evaluated by immunohistochemistry and quantified by digital image analysis with comparison to RP tissue from untreated prostate cancer patients as controls. Results: 18 patients were evaluated with 6 patients at each dose level. Treatment with GM-CSF was associated with an increase in the number of myeloid cells including myeloid dendritic cells. Treatment was also associated with increases in circulating conventional CD4 and CD8 T cells and NK cells. The number of FoxP3+ regulatory CD4+ T cells was also increased, but to a much lower magnitude. At the time of radical prostatectomy, treatment was associated with a recruitment of CD3+ T cells to the tumor rim, and with cohort 3, at the centers of tumor. These T cells were predominantly CD8+ T cells, although conventional CD4+ T cells were also increased. No increase in monocytes or dendritic cells was seen in the tissue. Conclusion: Daily injection of systemic GM-CSF induces an increase in circulating antigen presenting cells as well as T and NK cells. While this treatment does not enhance the frequency of antigen presenting cells in the tumor microenvironment, this treatment recruits effector CD8+ T cells into the tumor rims. Citation Format: Xiao X. Wei, Stephen Chan, Jera Lewis, Serena Kwek, Vinh Dao, Lawrence Fong. Recruitment of effector T cells into the tumor rim and center with neoadjuvant systemic GM-CSF in patients with localized prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 276. doi:10.1158/1538-7445.AM2015-276
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call