The number of regulatory T cells in prostate cancer is associated with the androgen receptor and hypoxia-inducible factor (HIF)-2alpha but not HIF-1alpha.
BACKGROUND
Regulatory T cells (T(R)) mediate peripheral immunological tolerance and are implicated in tumor progression. Because prostate cancer is being investigated for treatment by immunotherapy, we have assessed tumor T(R) in prostate cancers.


METHODS
T(R) cells were identified by FOXP3 in tissue microarrays (TMAs) from 146 radical prostatectomies and correlated with clinicopathological tumor parameters and prostatic specific antigen rise (PSA).


RESULTS
Twenty of 146 tumors contained no T(R). The mean of the average for the remaining 146 patients was 7.24. There was a significant correlation between T(R) and androgen receptor (P=0.003) and with hypoxia-inducible factor (HIF)-2alpha (P=0.007) but not HIF-1alpha (P=0.25). There was no significant correlation between T(R) numbers and stage, capsular invasion, urethral margins, vascular invasion, Gleason score, pre-operative PSA, or time to PSA recurrence (all P>0.05).


CONCLUSIONS
T(R) in prostate tumors shows significant heterogeneity and may be the result of hormonal and hypoxic signaling. Targeting these may reduce T(R) in tumors allowing more successful immune therapies.
Fox
Stephen B
SB
Department of Pathology, Peter MacCallum Cancer Centre, St Andrews Place, Melbourne, Australia. stephen.fox@petermac.org
Launchbury
Rosalind
R
Bates
Gaynor J
GJ
Han
Cheng
C
Shaida
Nadeem
N
Malone
Peter R
PR
Harris
Adrian L
AL
Banham
Alison H
AH
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D011467:Prostate / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D017430:Prostate-Specific Antigen; D011944:Receptors, Androgen; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1; C410798:AR protein, human; C418974:FOXP3 protein, human; C497442:HIF1A protein, human