CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients.
In this study, we investigated whether CD4+CD25high regulatory T cells (Treg) are increased in the tumor tissue and peripheral blood of early-stage prostate cancer patients undergoing prostatectomy. We show that the prevalence of CD4+CD25high T cells inside the prostate was significantly higher in the tumor compared with benign tissue from the same prostate. Furthermore, the frequency of CD4+CD25high T cells in peripheral blood was significantly higher in prostate cancer patients compared with normal donors. A proportion of the CD4+CD25high T cells was also shown to be glucocorticoid-induced TNF receptor, ICOS, and FOXP3 positive. Moreover, CD4+CD25+ T cells from blood and supernatants from cultured prostate tumor tissue samples exhibited immunosuppressive function in vitro. Furthermore, supernatants from cultured prostate tissue samples and prostate cancer ascites fluid induced migration of CD4+CD25+ T cells and were shown to contain the regulatory T cell chemokine CCL22 by ELISA. Our findings indicate that Tregs are an important cellular component of early-stage prostate tumors, and thus new therapeutic strategies aimed at inhibition or depletion of Tregs may improve prostate cancer immunotherapy.
Miller
Ashley M
AM
Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Karonlinska Institute, Stockholm, Sweden. Ashley.Miller@ki.se
Lundberg
Kajsa
K
Ozenci
Volkan
V
Banham
Alison H
AH
Hellström
Magnus
M
Egevad
Lars
L
Pisa
Pavel
P
D000368:Aged; D001201:Ascites / Q000276:immunology / Q000473:pathology; D018791:CD4 Lymphocyte Count; D045744:Cell Line, Tumor; D002474:Cell-Free System / Q000276:immunology / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D006131:Growth Inhibitors / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis* / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D006131:Growth Inhibitors; D053645:Interleukin-2 Receptor alpha Subunit