Paucity of PD-L1 expression in prostate cancer: Innate and adaptive immune resistance

A. M. Martin, T. R. Nirschl, C. J. Nirschl, B. J. Francica, C. M. Kochel, A. Van Bokhoven, A. K. Meeker, M. S. Lucia, R. A. Anders, A. M. Demarzo, C. G. Drake

Research output: Contribution to journalArticle

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Abstract

BACKGROUND:Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation - constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss.METHODS:Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples.RESULTS:In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss.CONCLUSIONS:These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

Original languageEnglish (US)
Pages (from-to)325-332
Number of pages8
JournalProstate Cancer and Prostatic Diseases
Volume18
Issue number4
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Prostatic Neoplasms
Ligands
Phosphoric Monoester Hydrolases
Cell Line
Prostate
Tensins
Neoplasms
Flow Cytometry
Up-Regulation
Western Blotting
Clinical Trials
Staining and Labeling
Cytokines
T-Lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

Cite this

Martin, A. M., Nirschl, T. R., Nirschl, C. J., Francica, B. J., Kochel, C. M., Van Bokhoven, A., ... Drake, C. G. (2015). Paucity of PD-L1 expression in prostate cancer: Innate and adaptive immune resistance. Prostate Cancer and Prostatic Diseases, 18(4), 325-332. https://doi.org/10.1038/pcan.2015.39

Paucity of PD-L1 expression in prostate cancer : Innate and adaptive immune resistance. / Martin, A. M.; Nirschl, T. R.; Nirschl, C. J.; Francica, B. J.; Kochel, C. M.; Van Bokhoven, A.; Meeker, A. K.; Lucia, M. S.; Anders, R. A.; Demarzo, A. M.; Drake, C. G.

In: Prostate Cancer and Prostatic Diseases, Vol. 18, No. 4, 01.12.2015, p. 325-332.

Research output: Contribution to journalArticle

Martin, AM, Nirschl, TR, Nirschl, CJ, Francica, BJ, Kochel, CM, Van Bokhoven, A, Meeker, AK, Lucia, MS, Anders, RA, Demarzo, AM & Drake, CG 2015, 'Paucity of PD-L1 expression in prostate cancer: Innate and adaptive immune resistance', Prostate Cancer and Prostatic Diseases, vol. 18, no. 4, pp. 325-332. https://doi.org/10.1038/pcan.2015.39
Martin, A. M. ; Nirschl, T. R. ; Nirschl, C. J. ; Francica, B. J. ; Kochel, C. M. ; Van Bokhoven, A. ; Meeker, A. K. ; Lucia, M. S. ; Anders, R. A. ; Demarzo, A. M. ; Drake, C. G. / Paucity of PD-L1 expression in prostate cancer : Innate and adaptive immune resistance. In: Prostate Cancer and Prostatic Diseases. 2015 ; Vol. 18, No. 4. pp. 325-332.
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abstract = "BACKGROUND:Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation - constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss.METHODS:Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples.RESULTS:In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss.CONCLUSIONS:These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.",
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T1 - Paucity of PD-L1 expression in prostate cancer

T2 - Innate and adaptive immune resistance

AU - Martin, A. M.

AU - Nirschl, T. R.

AU - Nirschl, C. J.

AU - Francica, B. J.

AU - Kochel, C. M.

AU - Van Bokhoven, A.

AU - Meeker, A. K.

AU - Lucia, M. S.

AU - Anders, R. A.

AU - Demarzo, A. M.

AU - Drake, C. G.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - BACKGROUND:Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation - constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss.METHODS:Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples.RESULTS:In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss.CONCLUSIONS:These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

AB - BACKGROUND:Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation - constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss.METHODS:Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples.RESULTS:In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss.CONCLUSIONS:These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.

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