Boosting immune response with GM-CSF optimizes primary cryotherapy outcomes in the treatment of prostate cancer: a prospective randomized clinical trial

Prostate Cancer Prostatic Dis. 2021 Sep;24(3):750-757. doi: 10.1038/s41391-021-00321-8. Epub 2021 Feb 8.


Objective: 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.

Materials and methods: 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.

Results: 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).

Conclusions: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Combined Modality Therapy
  • Cryotherapy / mortality*
  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Prognosis
  • Prospective Studies
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Survival Rate


  • Granulocyte-Macrophage Colony-Stimulating Factor