Division of Urology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Clinical Research and Trials Unit, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Prostate Cancer Prostatic Dis. 2021 Sep;24(3):750-757. doi: 10.1038/s41391-021-00321-8. Epub 2021 Feb 8.
We explored the association of prostate cryotherapy and immunomodulation with granulocyte-macrophage colony-stimulating factor (GMCSF) in the generation of detectable tumor-specific T- and B-cell responses in men with prostate cancer.
A randomized pilot study of patients assigned to either cryotherapy alone (Control group) or in combination with GMCSF (Treatment group). The impact of therapy on the development of T- and B-cell responses against tumor-related antigens was studied using enzyme-linked immune absorbent spot (ELISpot) and protein microarray panels (Sematrix) assays, respectively. Fold changes in response to treatment were calculated by normalization of post-treatment ELISpot values against the mean pre-cryoablation response. Student t tests between treatment and control groups at 4 weeks and 12 weeks across all the antigens were performed.
A total of 20 patients were randomized to either control or treatment arm. At 4 weeks after cryotherapy, the treatment group demonstrated an average fold change in cancer antigen-related antibodies of 2.8% above their mean baseline values, whereas controls averaged an 18% change below mean baseline (p < 0.05). At 12 weeks, antibody response in treatment group increased to 25% above baseline, while the average of control group patients remained 9% below baseline (p < 0.05). Patients in treatment group displayed, on average, higher ELISPOT readings for the 4- and 12-week times points (527 vs 481 for PSA and 748 vs 562 for PAP).
GMCSF appeared to broadly elevate antibodies against prostate-specific and nonspecific antigens. Prostate antigen-specific T-cell responses were more enhanced over non-prostate-specific responses, preferentially in the treatment group. Our findings suggest a possible therapeutic effect of adjuvant immunotherapy in association with cryotherapy for the treatment of prostate cancer.
我们探讨了前列腺冷冻治疗和免疫调节与粒细胞-巨噬细胞集落刺激因子（GMCSF）在产生前列腺癌患者可检测到的肿瘤特异性 T 细胞和 B 细胞反应中的关联。
一项对患者进行的随机试点研究，将患者分为单独接受冷冻治疗（对照组）或联合 GMCSF 治疗（治疗组）。使用酶联免疫吸附斑点（ELISpot）和蛋白质微阵列（Sematrix）检测试剂盒，分别研究治疗对针对肿瘤相关抗原的 T 细胞和 B 细胞反应的影响。通过将治疗后 ELISpot 值与冷冻前的平均反应值进行归一化，计算出对治疗的反应的倍数变化。在所有抗原的 4 周和 12 周时，对治疗组和对照组之间的学生 t 检验进行了比较。
共有 20 名患者被随机分配到对照组或治疗组。在冷冻治疗后 4 周，治疗组的癌症相关抗原相关抗体的平均倍数变化比其平均基线值高 2.8%，而对照组的平均变化比平均基线值低 18%（p<0.05）。在 12 周时，治疗组的抗体反应增加到基线以上 25%，而对照组患者的平均反应仍低于基线 9%（p<0.05）。治疗组患者在 4 周和 12 周时的 ELISPOT 读数平均更高（PSA 为 527 对 481，PAP 为 748 对 562）。
GMCSF 似乎广泛提高了针对前列腺特异性和非特异性抗原的抗体。与非前列腺特异性反应相比，前列腺抗原特异性 T 细胞反应得到了更增强，特别是在治疗组中。我们的发现表明，在与冷冻治疗联合应用时，辅助免疫疗法可能对前列腺癌的治疗有一定的治疗效果。
