Dysfunction of PSA-specific CD8+ T cells in prostate cancer patients correlates with CD38 and Tim-3 expression.
The efficacy of immunotherapy in cancer patients is influenced by differences in their immune status. An evaluation of immunocompetence before therapy may help to predict therapeutic success and guide the selection of appropriate regimens. We assessed the preexisting cellular immunity against prostate-specific antigen (PSA) in untreated prostate cancer patients and healthy controls through measurement of the phenotype and function of CD8(+) T cells. Our data show that the majority of healthy men possess functional PSA-specific CD8(+) T cells in contrast to cancer patients, where <50 % showed a CD8(+) T cell response. PSA146-154-specific CD8(+) T cells of these patients had a higher expression of the activation marker CD38 and the exhaustion marker Tim-3, indicating that PSA-specific cells are exhausted. The heterogeneity of the CD8(+) T cell response against PSA in prostate cancer patients may influence their response to therapy and is a factor to be taken into account while designing and selecting treatment regimens.
Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13353, Berlin, Germany.
Alberto Sada
AS
Japp
Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13353, Berlin, Germany.
M Alper
MA
Kursunel
Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13353, Berlin, Germany.
Sarah
S
Meier
Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13353, Berlin, Germany.
Julia N
JN
Mälzer
State Key Laboratory of Agro-Biotechnology China, Agricultural University, Beijing, 100193, China.
Xiangdong
X
Li
Department of Physiology, Faculty of Medicine, Institute of Biomedicine, University of Turku, 20520, Turku, Finland.
Nafis A
NA
Rahman
Department of Urology, Charité University Medicine, 10117, Berlin, Germany.
Waltraut
W
Jekabsons
Department of Urology, Charité University Medicine, 10117, Berlin, Germany.
Hans
H
Krause
Department of Urology, Charité University Medicine, 10117, Berlin, Germany.
Ahmed
A
Magheli
Department of Urology, Charité University Medicine, 10117, Berlin, Germany.
Christian
C
Klopf
Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13353, Berlin, Germany.
Andreas
A
Thiel
Regenerative Immunology and Aging, Berlin-Brandenburg Center for Regenerative Therapies, CVK Charité University Medicine, Föhrerstr. 15, 13353, Berlin, Germany. marco.frentsch@charite.de.
Marco
M
Frentsch
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis*; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000628:therapy
C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D017430:Prostate-Specific Antigen
Antigen-specific T cells; Exhaustion; PSA; Prostate cancer