Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+

Research output: Contribution to journalArticle

Abstract

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 β chain variable region (Vβ) gene sequences in both the peripheral blood and prostates of cancer patients. Vβ repertoire analysis was performed by family-specific Vβ 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 Vβ 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.

Original languageEnglish (US)
Pages (from-to)1694-1703
Number of pages10
JournalProstate
Volume69
Issue number15
DOIs
StatePublished - Nov 1 2009

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Prostate
Prostatic Neoplasms
T-Cell Antigen Receptor
T-Lymphocytes
Antigens
Programmed Cell Death 1 Receptor
Flow Cytometry
T-Cell Receptor Genes
Adaptive Immunity
Immunotherapy
Sequence Analysis
Organism Cloning
Membrane Proteins
Cell Death
Clone Cells
Inflammation
Phenotype
Genes
Neoplasms

Keywords

  • CD8+ T-cell
  • Inflammation
  • Oligoclonal
  • PD-1
  • Prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. / Sfanos, Karen; Bruno, Tullia C.; Meeker, Alan Keith; Demarzo, Angelo Michael; Isaacs, William B; Drake, Charles G.

In: Prostate, Vol. 69, No. 15, 01.11.2009, p. 1694-1703.

Research output: Contribution to journalArticle

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abstract = "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 β chain variable region (Vβ) gene sequences in both the peripheral blood and prostates of cancer patients. Vβ repertoire analysis was performed by family-specific Vβ 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 Vβ 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.",
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T1 - Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+

AU - Sfanos, Karen

AU - Bruno, Tullia C.

AU - Meeker, Alan Keith

AU - Demarzo, Angelo Michael

AU - Isaacs, William B

AU - Drake, Charles G.

PY - 2009/11/1

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N2 - 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 β chain variable region (Vβ) gene sequences in both the peripheral blood and prostates of cancer patients. Vβ repertoire analysis was performed by family-specific Vβ 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 Vβ 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.

AB - 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 β chain variable region (Vβ) gene sequences in both the peripheral blood and prostates of cancer patients. Vβ repertoire analysis was performed by family-specific Vβ 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 Vβ 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.

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