Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+.
BACKGROUND
Prostate-infiltrating CD8(+) T lymphocytes (CD8(+) PIL) are prevalent in men with prostate cancer (PCa), however, it is unclear whether the presence of such cells reflects a non-specific immune infiltrate or an oligoclonal, antigen-driven adaptive immune response.


METHODS
We investigated the complexity of the T-cell receptor (TCR) repertoire in the prostate gland by examining the diversity of CD8(+) TCR beta chain variable region (Vbeta) gene sequences in both the peripheral blood and prostates of cancer patients. Vbeta repertoire analysis was performed by family-specific Vbeta spectratyping and flow cytometry, as well as direct sequence analysis (5' RACE and cloning). Programmed cell death 1 (PD-1 or PDCD1) expression on peripheral blood CD8(+) T cells and CD8(+) PIL was analyzed by flow cytometry.


RESULTS
CD8(+) PIL isolated from cancer patients exhibited restricted TCR Vbeta gene usage, and identical clones were identified in multiple sites within the prostate. Furthermore, CD8(+) PIL express high levels of the inhibitory receptor PD-1, a cell surface protein associated with an "exhausted" CD8(+) T-cell phenotype.


CONCLUSIONS
CD8(+) PIL appear to have undergone clonal expansion in response to an as yet unidentified antigen; however, due to the high expression of PD-1, these cells are likely incapable of mounting an effective immune response. The results provide an important basis for further efforts aimed at the identification of specific antigens involved in prostatic inflammation, and suggest that PD-1 blockade may be useful in immunotherapy for PCa.
Sfanos
Karen S
KS
Department of Pathology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21231, USA.
Bruno
Tullia C
TC
Meeker
Alan K
AK
De Marzo
Angelo M
AM
Isaacs
William B
WB
Drake
Charles G
CG
D000230:Adenocarcinoma / Q000276:immunology*; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000473:pathology; D061026:Programmed Cell Death 1 Receptor; D011471:Prostatic Neoplasms / Q000276:immunology*; D019105:Random Amplified Polymorphic DNA Technique; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell