Expression of PD-L1 in tumor-associated nerves correlates with reduced CD8+ tumor-associated lymphocytes and poor prognosis in prostate cancer.
Int J Cancer
; 144(12): 3099-3110, 2019 06 15.
Article
em En
| MEDLINE
| ID: mdl-30537104
To investigate immune profile consisting of stromal PD-L1 expression, inhibitory or non-T-cell inflamed tumor microenvironment that may predict response to anti-PD-L1/PD-1 immunotherapy in prostate cancer, we validated the specificity of a PD-L1 monoclonal antibody (E1L3N) and identified PD-L1 specific expression in prostatic stromal nerve cells. PD-L1 expression was analyzed in 73 primary prostate cancers and 7 castration-resistant prostate cancers (CRPC) by immunohistochemistry (IHC) and resulting data from primary prostate cancers were correlated with tumor-associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD-L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. However, PD-L1 was frequently observed in the nerve branches in the tumor-associated stroma (69 of 73 cases, 94.5%), supported by colocalization with axonal marker PGP9.5. FoxP3-, CD3- and CD8-positive T lymphocytes were observed in 74.6% (47/63), 98.4% (62/63) and 100% (61/61) of the cases, respectively. The density of PD-L1+ tumor-associated nerves (TANs) was inversely correlated with that of CD8+ TALs. Higher density of PD-L1+ TANs was significantly associated with biochemical recurrence (BCR) in Kaplan-Meier survival analysis (p = 0.016). In both univariate and multivariate Cox analysis, the density of PD-L1+ TANs was independently prognostic of BCR. In conclusion, PD-L1 expression is rare in prostate tumor cells but prevalent in TANs and negatively correlated with CD8+ TALs. Neuro-immunological interaction may be a contribution to immune-suppressive microenvironment. Combinatorial treatment regimen designs to neural PD-L1 and TALs should be warranted in future clinical application of anti-PD-L1/PD-1 immunotherapy in prostate cancer.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Próstata
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Neoplasias da Próstata
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Linfócitos T CD8-Positivos
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Antígeno B7-H1
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Neoplasias de Próstata Resistentes à Castração
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article