Interaction of Programmed Death-1 and Programmed Death-1 Ligand-1 Contributes to Testicular Immune Privilege

Cheng, Xuyang; Dai, Hehua; Ni, Wan; Moore, Yolonda; Vankayalapati, Ramakrishna; Dai, Zhenhua

doi:10.1097/tp.0b013e3181a75633

Cited by 64 publications

(59 citation statements)

References 61 publications

(68 reference statements)

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“…Testicular tissue is an immunologically privileged site with naturally suppressed immune responses mediated by PD-1: PD-L1 negative co-stimulation [32]. The role of PD-L1 in testicular immune privilege and homeostasis of immune responses has been therefore clearly identified [32].…”

Section: Discussionmentioning

confidence: 99%

Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors

et al. 2017

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PurposeTesticular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative in a small subgroup of patients. Previously, we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. This study aimed to evaluate the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs.ResultsPD-L1 positive TILs were found significantly more often in seminomas (95.9% of patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%), choriocarcinomas (54.5%) or teratomas (35.7%) (All p < 0.05). TGCTs patients with high infiltration of PD-L1 positive TILs (HS ≥ 160) had significantly better progression-free survival (HR = 0.17, 95% CI 0.09 – 0.31, p = 0.0006) and overall survival (HR = 0.08, 95% CI 0.04 – 0.16, p = 0.001) opposite to patients with lower expression of PD-L1 (HS < 150). PD-1 expressing TILs were not prognostic in TGCTs.Materials and MethodsSurgical specimens from 240 patients with primary TGCTs were included into this translational study. The PD-1 and PD-L1 expression on tumor and TILs were detected by immunohistochemistry using anti-PD-1 and anti-PD-L1 monoclonal antibody. Scoring was performed semiquantitatively by weighted histoscore (HS) method.ConclusionsThe prognostic value of PD-L1 expressing TILs in TGCTs was demonstrated for the first time.

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Section: Discussionmentioning

confidence: 99%

Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors

et al. 2017

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“…76 It is constitutively expressed in the testis and involved in the survival of islet allografts, suggesting that the PD-1/PD-L1 system is a mechanism that underlies testicular immune privilege. 77 The growth arrest-specific gene 6 (Gas6)/Protein S (ProS)-Tyro3, Axl and Mer (TAM) system is a negative regulatory immune system. 78 We showed that TAM receptor tyrosine kinases and their common ligands, Gas6 and ProS, regulate immune homeostasis in the mouse testis.…”

Section: Immune Privilege In the Testismentioning

confidence: 99%

Testicular defense systems: immune privilege and innate immunity

et al. 2014

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The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation.

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“…PD-1 is expressed in T cells, and its activation by PD-L1 mediates T cell tolerance (Keir et al, 2006). An recent study demonstrated that PD-L1 is constitutively expressed in the testis and contributes to the long-term survival of islet allografts transplanted in the testis, suggesting that PD-1/PD-L1 system may represents a mechanism of testicular immune privilege (Cheng et al, 2009).…”

Section: Local Immunosuppression Mechanismsmentioning

confidence: 98%

Mechanisms of testicular immune privilege

2011

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The testis exhibits a distinctive form of immune privilege to protect the germ cells from the host immune attack. The property of testicular immune privilege was originally attributed to the blood-testis barrier in the seminiferous epithelium, which sequesters antigens. Recent studies have uncovered several levels of immune control besides the blood-testis barrier involved in the privilege of the testis, including the mechanisms of immune tolerance, reduced immune activation, localized active immunosuppression and antigen-specific immunoregulation. The somatic cells of the testis, especially Sertoli cells, play a key role in regulating the testicular immune privileged status. The constitutive expression of anti-inflammatory factors in the testis by somatic cells is essential for local immunosuppression. Growing evidence shows that androgens orchestrate the inhibition of proinflammatory factors and shift cytokine balance toward a tolerogenic environment. Disruption of these protective mechanisms, which may be caused by trauma, infection and genetic factors, can lead to orchitis and infertility. This review article highlights the unique immune environment of the testis, particularly focuses on the regulation of testicular immune privilege.

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Interaction of Programmed Death-1 and Programmed Death-1 Ligand-1 Contributes to Testicular Immune Privilege

Abstract: The constitutive expression of PD-L1 in the testis is an important mechanism underlying testicular immune privilege and long-term survival of intratesticular islet allografts.

Cited by 64 publications

References 61 publications

Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors

Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors

Testicular defense systems: immune privilege and innate immunity

Mechanisms of testicular immune privilege

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