Systemic GM-CSF Recruits Effector T Cells into the Tumor Microenvironment in Localized Prostate Cancer.
Systemic GM-CSF Recruits Effector T Cells into the Tumor Microenvironment in Localized Prostate Cancer.
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DOI：
10.1158/2326-6066.cir-16-0042
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发表时间：
2016-11
影响因子：
10.1
通讯作者：
Fong L
中科院分区：
文献类型：
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作者：
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
粒细胞-巨噬细胞集落刺激因子（GM-CSF）在癌症疫苗试验中用作佐剂，并有可能通过免疫疗法增强抗肿瘤疗效;然而，其免疫学效应尚未完全了解。在这里，我们报告了一项新辅助GM-CSF治疗行根治性前列腺癌切除术的局限性前列腺癌患者的I期研究结果。患者每天接受皮下注射GM-CSF（250 µg/m2/天），持续2周（队列1; n = 6）、3周（队列2; n = 6）或4周（队列3; n = 6）。治疗耐受性良好，所有1级或2级不良事件。两名患者的前列腺特异性抗原（PSA）下降超过50%。GM-CSF治疗增加了循环成熟髓样树突细胞、增殖常规CD 4 T细胞、增殖CD 8 T细胞和较小数量级FoxP 3+调节性CD 4 T细胞的数量。虽然GM-CSF治疗没有增加抗原呈递细胞在前列腺的定位，但治疗与CD 8 + T细胞向肿瘤的募集有关。这些结果表明，全身GM-CSF可以调节肿瘤微环境中的T细胞浸润。
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 1 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.