Recent Insight into the Role of the <scp>PD</scp>‐1/<scp>PD</scp>‐L1 Pathway in Feto‐Maternal Tolerance and Pregnancy

Zhang, Yonghong; Tian, Miao; Tang, Manshu; Liu, Zhaozhao; Liao, Aihua

doi:10.1111/aji.12365

Cited by 67 publications

(61 citation statements)

References 39 publications

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“…Although larger prospective analyses are still needed to validate this association, detection and diagnosis of cutaneous reactions during anti-PD-1 therapy gain further importance in this context. By inhibiting T-cell activation and sustaining Tregs (24), the PD-1/PD-L pathway plays a major role in peripheral tolerance, including transplant (25) and feto-maternal tolerance (26). The concept of a tolerogenic role for PD-1/PD-1L has emerged from observations that PD-1-deficient mice develop autoimmune pathologies (27), including lichenoid reactions (22).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy

Goldinger

Stieger

Meier

et al. 2016

Clinical Cancer Research

176

149

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Purpose: Immunotherapy has experienced impressive progress in cancer treatment. Antibodies against PD-1 improved survival in different types of cancer including melanoma. They are generally well tolerated. However, skin toxicities including pruritus, rashes, and vitiligo are reported. Although frequent, they have not been characterized further yet. In this analysis, we aimed to systematically assess and characterize the adverse cutaneous reactions observed in patients with melanoma treated with anti-PD-1 antibodies. Experimental Design: Patients with melanoma were treated with anti-PD-1 antibodies within clinical trials and an early-access program. Adverse cutaneous eruptions that emerged in our melanoma patient cohort were systematically investigated and classified using histology and gene expression profiling in comparison with maculopapular drug rash, cutaneous GVHD, and the severe drug eruption toxic epidermal necrolysis (TEN). Results: Between February 2013 and September 2015, 68 patients with stage IV melanoma were treated at the University Hospital Zurich (Zurich, Switzerland); 15 patients (22%) developed cutaneous reactions and 10 (15%) vitiligo. The cutaneous reactions ranged from small erythematous papules with mild pruritus to disseminated erythematous maculopapular rashes (MPR) without signs of epidermal involvement to severe MPRs, including epidermal detachment and mucosal involvement. Although skin involvement varied from mild rash to bullous drug eruptions, gene expression profiling pathogenically classified all investigated cases as TEN-like reactions. Conclusions: As predicted by the PD-1 knockout mouse, anti-PD-1 antibodies frequently cause adverse cutaneous reactions. Gene expression profiling reminds in all cases of a TEN-like pattern, suggesting that PD-1/PD-L1 interaction is required to preserve epidermal integrity during inflammatory skin reactions. Clin Cancer Res; 22(16); 4023–9. ©2016 AACR.

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Section: Discussionmentioning

confidence: 99%

Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy

Goldinger

Stieger

Meier

et al. 2016

Clinical Cancer Research

176

149

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“…The functions and mechanisms for broad PD-L1 expression on T cells from the FRT are unknown and may be different depending on anatomical location. For example, T cells in the endometrium may up-regulate PD-L1 in response to the tolerogenic tissue environment, rich in TGF-β and IL-10 [25–27], and may be up-regulated to mediate potential interactions with PD-1-expressing cells from the trophoblast to prevent rejection [18, 28]. In contrast, T cells in the cervix and specially the ectocervix are exposed to a higher load of commensals and potential pathogens, which may mediate PD-L1 up-regulation [29].…”

Section: Discussionmentioning

confidence: 99%

“…PD-1 binding to PD-L1 attenuates immune responses and limits immune-mediated tissue damage [16, 17]. The PD-1/PD-L1 pathway is also up-regulated during pregnancy to prevent rejection [18, 19]. Pathological conditions, such as cancer or chronic infections, also exploit this pathway to suppress protective T cell responses [15, 16].…”

Section: Introductionmentioning

confidence: 99%

Menopausal status influences the expression of programmed death (PD)‐1 and its ligand PD‐L1 on immune cells from the human female reproductive tract

Shen

Rodriguez-García

Patel

et al. 2016

American J Rep Immunol

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The PD-1/PD-L1 pathway regulates peripheral tolerance, immune responses, and is up-regulated in chronic viral infections, including HIV infection. However, expression of PD-1/PD-L1 on immune cells from the human female reproductive tract (FRT), and possible regulation by menopause and sex hormones are poorly understood. We analyzed PD-1/PD-L1 expression on CD4+ and CD8+ T cells, CD163+ macrophages, and CD11c+ dendritic cells (DC) from endometrium (EM), endocervix (CX) and ectocervix (ECX). PD-1 and PD-L1 were constitutively expressed on CD4+ and CD8+ T cells from EM, CX and ECX. PD-L1+CD4+ T cells were increased in CX compared to EM and ECX, while no differences were found for PD-1 or between CD8+ T cells from different sites. Macrophages and DCs constitutively expressed PD-L1, but not PD-1, with no differences observed between FRT sites. Premenopausal FRT tissues showed increased PD-L1 expression on CD8+ T cells but decreased expression on DCs when compared to postmenopausal women. In vitro estradiol treatment up-regulated PD-L1 expression on CD8+ T cells from CX, but not EM or ECX, and had no effect on PD-1/PD-L1 expression on the other cell types. Our results suggest that PD-L1 may be involved in the differential regulation of FRT immune responses between premenopausal and postmenopausal women.

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“…PD-1 was reported to be mainly expressed on hematopoietic cells, including activated T cells, B cells, myeloid dendritic cells, activate monocytes/macrophage, and natural killer T cells. 29 Decidual stromal cells can suppress CD4 + T-cell pro-inflammatory cytokine production via the PD-1/PD-L pathway, which helps to regulate a balanced cytokine milieu at the maternal-fetal interface. 20 Engagement of PD-1/PD-L1 delivers co-inhibitory signals into PD-1 + T cells, mainly promoting the development and function of Tregs and suppressing effector T-cell-mediated immune responses.…”

Section: Introductionmentioning

confidence: 99%

“…20 Engagement of PD-1/PD-L1 delivers co-inhibitory signals into PD-1 + T cells, mainly promoting the development and function of Tregs and suppressing effector T-cell-mediated immune responses. 29 Several researchers have also and MHC-II in response to IFN-γ in vitro, directly inhibiting CD8 + T-cell proliferation through PD-L1. 21 Aside from their membrane-bound forms, PD-1 and PD-L1 also have soluble forms: soluble PD-1 (sPD-1) and soluble PD-L1 (sPD-L1).…”

Section: Introductionmentioning

confidence: 99%

Identification of programmed cell death 1 and its ligand in the testicular tissue of mice

Wang

Duan

et al. 2019

American J Rep Immunol

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Problem This study aims to determine the expression and localization of programmed cell death 1 (PD‐1) and programmed cell death 1 ligand 1 (PD‐L1) in the testes of mice at different developmental stages. Method of study By means of RT‐qPCR, Western blot and immunofluorescence, the expression and localization of PD‐1 and PD‐L1 were detected in the testicular tissues of mice at different postnatal times: P7, P14, P21, P28, P35, and adulthood. Meanwhile, the level of soluble PD‐L1 (sPD‐L1) was evaluated by ELISA in the testicular interstitial fluid (IF) of the adult mice, culture supernatants of TM4 cell lines (Sertoli cells lines), and primary Sertoli cells at P14. Results Pd‐1 mRNA levels were unexpectedly low. From P7 to P21, there was limited PD‐1 protein detected while PD‐1 was evident at P28 and afterward at significantly higher levels than at P14 and P21 (P < 0.05). Despite being found in the interstitial area at P7, P14, and P21, PD‐1 was also detected in the germ cells of the seminiferous tubules after P28. Pd‐l1 mRNA exhibited age‐related changes, peaking at P21, while PD‐L1 protein was constitutively expressed at any stage, specifically localized in the nucleus of Sertoli cells. Moreover, the level of sPD‐L1 in IF was significantly higher than that in the culture supernatants of both TM4 and primary Sertoli cells at P14. Conclusions PD‐1 and PD‐L1 were present in the testicular tissue of adult mice. The expression and localization of PD‐1 fluctuated with age, and PD‐1 was mainly localized to advanced germ cells, suggesting that it may play a role in spermiogenesis. PD‐L1 was constitutively expressed in the nucleus of Sertoli cells, which could secrete sPD‐L1 into the testicular interstitial space and thus may be involved in testicular immune privilege.

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Recent Insight into the Role of the PD‐1/PD‐L1 Pathway in Feto‐Maternal Tolerance and Pregnancy

Cited by 67 publications

References 39 publications

Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy

Cytotoxic Cutaneous Adverse Drug Reactions during Anti-PD-1 Therapy

Menopausal status influences the expression of programmed death (PD)‐1 and its ligand PD‐L1 on immune cells from the human female reproductive tract

Identification of programmed cell death 1 and its ligand in the testicular tissue of mice

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