PD-1 receptor on immune cells, its expression and potential role in cancer therapy

Elezov, Dmitry S.; Kudryavtsev, I. V.

doi:10.18620/ctt-1866-8836-2019-8-2-8-16

Cited by 4 publications

(3 citation statements)

References 64 publications

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“…Thus, we first addressed in vitro the cross-activity between anti-human PD-1 (pembrolizumab) and chicken PD-1. In fact, PD-1 expression is absent or low on the surface of resting immune cells but can be induced in different immune populations such as CD4 + and CD8 + T cells, NK cells, B cells, macrophages, and some dendritic cell (DC) subsets [38][39][40]. The use of anti-CD3 and IL2 for human T cell activation has been reported for many years [41,42], as well as in the mouse model [43].…”

Section: Discussionmentioning

confidence: 99%

PD-1/PD-L1 Checkpoint Inhibitors Are Active in the Chicken Embryo Model and Show Antitumor Efficacy In Ovo

Wang¹,

Rousset²,

Prunier³

et al. 2022

Cancers

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(1) Purpose: To assess the use of the chicken embryo (in ovo) model as an alternative in vivo model for immuno-oncology (IO) drug development, focusing on programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors. (2) Methods: First, the presence of immune cells in the model was detected through the immunophenotyping of chicken peripheral blood mononuclear cells (PBMCs) based on fluorescence activated cell sorting (FACS) analysis and the immunohistochemistry (IHC) analysis of in ovo tumor-infiltrating lymphocytes. Second, the cross-reactivity between one anti-human PD-1 Ab, pembrolizumab (KEYTRUDA®), and chicken PD-1 was verified through the labelling of chicken splenocytes with pembrolizumab by FACS analysis. Third, the blockade effect of pembrolizumab on chicken PBMCs was assessed in vitro through cytotoxicity assay based on MTT. Fourth, the CAM assay was used to estimate the anti-tumor performance of pembrolizumab through the analyses of tumor growth and chicken immune cell infiltration in tumors. Finally, the efficacy of several PD-1 or PD-L1 inhibitors (nivolumab, atezolizumab and avelumab) on tumor growth was further assessed using the CAM assay. (3) Results: The presence of CD3+, CD4+, CD8+ T lymphocytes and monocytes was confirmed by FACS and IHC analyses. During in vitro assays, pembrolizumab cross-reacted with chicken lymphocytes and induced PD-1/PD-L1 blockade, which permitted the restoration of chicken T-cell’s cytotoxicity against human lung cancer H460 tumor cells. All these in vitro results were correlated with in ovo findings based on the CAM assay: pembrolizumab inhibited H460 tumor growth and induced evident chicken immune cell infiltration (with significant chicken CD45, CD3, CD4, CD8 and CD56 markers) in tumors. Furthermore, the potency of the CAM assay was not limited to the application of pembrolizumab. Nivolumab, atezolizumab and avelumab also led to tumor growth inhibition in ovo, on different tumor models. (4) Conclusions: The chicken embryo affords a physiological, immune reactive, in vivo environment for IO research, which allows observation of how the immune system defense against tumor cells, as well as the different immune tolerance mechanisms leading to tumor immune escape. The encouraging results obtained with PD-1/PD-L1 inhibitors in this study reveal the potential use of the chicken embryo model as an alternative, fast, and reliable in vivo model in the different fields of IO drug discovery.

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Section: Discussionmentioning

confidence: 99%

PD-1/PD-L1 Checkpoint Inhibitors Are Active in the Chicken Embryo Model and Show Antitumor Efficacy In Ovo

Wang¹,

Rousset²,

Prunier³

et al. 2022

Cancers

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“…GK-1 also increased the production of IFNγ and IL-2 in CD4 + T cells. These effects in the functional activity of T lymphocytes are accompanied by decreased levels of the inhibitory receptor PD-1 [ 44 ], an effect also observed. Altogether, these findings indicate that GK-1 could effectively enhance antitumor T cell immunity by promoting a robust, functionally active T cell infiltration into the breast tumor mass.…”

Section: Discussionmentioning

confidence: 98%

GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model

Hernández-Aceves,

Cervantes-Torres,

Torres-García

et al. 2023

Cancer Immunol Immunother

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Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties. Herein, GK-1 (5 mg/kg, i.v.) weekly administrated not only decreases tumor growth and the number of lung macro-metastases but also lung and lymph nodes micro-metastases. Histological analysis reveals that GK-1 reduced 57% of the intra-tumor vascular areas, diminished the leukemoid reaction's progression, and the spleens' weight and length. A significant reduction in VEGF-C, SDF-1, angiopoietin-2, and endothelin-1 angiogenic factors was induced. Moreover, GK-1 prevents T cell exhaustion in the tumor-infiltrating lymphocytes (TILs) decreasing PD-1 expression. It also increased IFN-γ and granzyme-B expression and the cytotoxic activity of CD8+ TILs cells against tumor cells. All these features were found to be associated with a better antitumor response and prognosis. Altogether, these results reinforce the potential of GK-1 to improve the clinical outcome of triple-negative breast cancer immunotherapy. Translation research is ongoing towards its evaluation in humans.

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“…Structurally PD-1 is a transmembrane protein and its interaction with ligands (PD-L1 or PD-L2) results in activation of PD-1/PD-L pathway [4,5]. This effect leads to downregulation of autoreactive T cells and upregulation of T regulatory cells [6].…”

Section: Clinical Studiesmentioning

confidence: 99%

Nivolumab in pediatric Hodgkin's lymphoma

Kozlov¹,

Kazantzev²,

Iukhta³

et al. 2019

CTT

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Immune checkpoint inhibitors (ICIs) are rather efficient in classical Hodgkin's lymphoma (cHL). Pembrolizumab (pembro) is approved in children and demonstrates high response rates with acceptable toxicity. The role of nivolumab (nivo) in pediatric cHL is only to be elucidated. The aim of the presented study was to assess safety and efficiency of nivo in this age group with relapsed or refractory (R-R) cHL. Twenty-one pediatric heavily pre-treated patients 9-18 years old received nivo-based therapy. Overall response was registered in 86% (complete response-57% and partial response-29%). Three-year overall survival (OS) and progression free survival (PFS) were 95% and 29%, respectively. Only 1 clinically significant adverse effect (AE) of nivo was registered in the study (autoimmune thyroiditis). We did not observe any unacceptable toxicity of nivo.

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PD-1 receptor on immune cells, its expression and potential role in cancer therapy

Cited by 4 publications

References 64 publications

PD-1/PD-L1 Checkpoint Inhibitors Are Active in the Chicken Embryo Model and Show Antitumor Efficacy In Ovo

PD-1/PD-L1 Checkpoint Inhibitors Are Active in the Chicken Embryo Model and Show Antitumor Efficacy In Ovo

GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model

Nivolumab in pediatric Hodgkin's lymphoma

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