Tumor infiltrating T lymphocytes expressing FoxP3, CCR7 or PD-1 predict the outcome of prostate cancer patients subjected to salvage radiotherapy after biochemical relapse

Cancer Biol Ther. 2016 Nov;17(11):1213-1220. doi: 10.1080/15384047.2016.1235666.


Tumor immunologic microenvironment is strongly involved in tumor progression and the presence of tumor infiltrating lymphocytes (TIL) with different phenotypes has been demonstrated to be of prognostic relevance in different malignancies. We investigated whether TIL infiltration of tumor tissues could also predict the outcome of prostate cancer patients. To this end, we carried out a retrospective analysis correlating the outcome of locally advanced prostate cancer patients undergone salvage radiotherapy upon relapse after radical surgery with the infiltration by different TIL populations. Twenty-two patients with resectable prostate cancer, with a mean age of 67 (+/-3.93) years, who received salvage radiotherapy with a mean of 69.66 (+/- 3.178) Gy in 8 weeks, between June 1999 and January 2009 and with a median follow up of 123 (+/- 55.82) months, were enrolled in this study. We evaluated, by immunohistochemistry, the intratumoral (t) and peripheral stroma (p) infiltration by CD45, CD3, CD4, CD8, CCR7, FoxP3 or PD-1-positive cells on tumor samples taken at the diagnosis (d) and relapse times (R). We correlated these variables with patients' biochemical progression free survival (bPFS), post-radiotherapy progression free survival (PFS), and overall survival (OS). Substantial changes in the rate of TIL subsets were found between the first and the second biopsy with progressive increase in CD4, CCR7, FoxP3, PD-1+ cells. Our analysis revealed that higher CD8p,R+ and lower PD-1R+ TIL scores correlated to a longer bPFS. Higher CD8p,R+ and CCR7t,R+ TIL scores and lower CD45p,R+ and FoxP3p,R+ TIL scores correlated to a prolonged PFS and OS. These results suggest that the immunological microenvironment of primary tumor is strictly correlated with patient outcome and provide the rationale for immunological treatment of prostate cancer.

Keywords: Chemokyne Receptor 7; FoxP3; PD-1; T regulators lymphocytes; disease-free survival; overall survival; prognosis; prostate cancer; radiotherapy; tumor infiltrating lymphocytes.

MeSH terms

  • Aged
  • Forkhead Transcription Factors / biosynthesis
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Programmed Cell Death 1 Receptor / biosynthesis
  • Programmed Cell Death 1 Receptor / immunology*
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Receptors, CCR7 / biosynthesis
  • Receptors, CCR7 / immunology*
  • Recurrence
  • Salvage Therapy / methods*
  • Tumor Microenvironment


  • CCR7 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CCR7