Evaluation of PD-1 and PD-L1 expression in canine urothelial carcinoma cell lines

Pinard, Chantale L.; Hocker, Samuel E; Poon, Andrew C.; Inkol, Jordon M.; Matsuyama, Arata; Wood, Richard D.; Wood, Geoffrey A.; Woods, J. Paul; Mutsaers, Anthony J.

doi:10.1016/j.vetimm.2021.110367

Cited by 12 publications

(13 citation statements)

References 34 publications

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“…103 Recently, PD-1 and PD-L1 expression profiles were measured in three different canine UC cell lines. The results showed a varying degree of protein and mRNA expression of both markers in all three cell lines, 104 indicating that immune checkpoint inhibition may be a treatment option in canine UC.…”

Section: Immune Checkpoint Moleculesmentioning

confidence: 93%

Role of the tumour microenvironment in bladder cancer pathogenesis and value of the reverse translational approach: a tale of two species

Ahmed,

Zdyrski,

Cheville

et al. 2023

Clinical and Translational Dis

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BackgroundBladder cancer is a significant malignancy in humans and canines, with high death rates and devastating clinical symptoms. Despite significant advances in therapeutic management over the years, only a small fraction of bladder cancer patients respond to immunotherapies as a second line of treatment. Since immunotherapies act on various cellular and molecular targets in the bladder cancer tumour microenvironment (TME), a greater understanding of the various types of immune cells, immune checkpoint molecules and cytokines involved in antitumour immunity will help to improve the success rate of current and novel immunotherapies, therefore enhancing the patients quality of life. Accumulating evidence shows fundamental similarities between human and canine muscle‐invasive bladder cancer (MIBC) in their clinical, histological and molecular features.AimThis review focuses on comparative aspects of MIBC in both species, highlighting the role that canines can play as a model for studying MIBC. Additionally, we discuss the various types of immune cells within bladder cancer TME that can influence the prognosis and response to immunotherapy and chemotherapy in both species.ConclusionIt remains challenging to recapitulate the heterogeneity and complexity of the bladder cancer tumour microenvironment using in vivo and in vitro models, such as zebrafish and 3D organoids models. Optimization of these techniques to create a more representative translational model has been facilitated through in vitro immune‐oncology cocultures, which are considered promising tools to help select the ideal individualized treatment options and predict disease prognosis.

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Section: Immune Checkpoint Moleculesmentioning

confidence: 93%

Role of the tumour microenvironment in bladder cancer pathogenesis and value of the reverse translational approach: a tale of two species

Ahmed,

Zdyrski,

Cheville

et al. 2023

Clinical and Translational Dis

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“…Western blotting (WB) for PD-L1 analysis was performed using recombinant PD-L1- Fc fusion protein (Sino Biological Europe GmbH, Eschborn, Germany), with cell lysates of K9TCC, K9TCC-SH (both kindly provided by Prof. Deborah Knapp, Purdue University, USA), and DH82 (ATCC), K9TCC, K9TCC-SH, and DH82. All cell lines were selected based on previous publications, which have shown that the cell lines expressed PD-1 and/or PD-L1 [ 27 , 30 , 31 ]. In addition, the K9TCC and K9TCC-SH were considered to have different levels of expression of EGFR [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

Development of Monoclonal Antibodies Targeting Canine PD-L1 and PD-1 and Their Clinical Relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma

Minoli

Licenziato

Kocikowski

et al. 2022

Cancers

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Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant chemotherapy, represents the standard of care for this tumor, but the outcome is generally poor, particularly for tumors diagnosed at an advanced stage. For this reason, novel treatment options are warranted, and a few recent reports have suggested the activation of the immune checkpoint axis in canine AGASACA. In our study, we developed canine-specific monoclonal antibodies targeting PD-1 and PD-L1. A total of 41 AGASACAs with complete clinical and follow-up information were then analyzed by immunohistochemistry for the expression of the two checkpoint molecules (PD-L1 and PD-1) and the presence of tumor-infiltrating lymphocytes (CD3 and CD20), which were evaluated within the tumor bulk (intratumor) and in the surrounding stroma (peritumor). Seventeen AGASACAs (42%) expressed PD-L1 in a range between 5% and 95%. The intratumor lymphocytes were predominantly CD3+ T-cells and were positively correlated with the number of PD-1+ intratumor lymphocytes (ρ = 0.36; p = 0.02). The peritumor lymphocytes were a mixture of CD3+ and CD20+ cells with variable PD-1 expression (range 0–50%). PD-L1 expression negatively affected survival only in the subgroup of dogs treated with surgery alone (n = 14; 576 vs. 235 days). The presence of a heterogeneous lymphocytic infiltrate and the expression of PD-1 and PD-L1 molecules support the relevance of the immune microenvironment in canine AGASACAs and the potential value of immune checkpoints as promising therapeutic targets.

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“…Currently, there is an increasing number of studies targeting PD-1/PD-L1 immune checkpoint inhibitors in human cancers including solid tumors and hematological malignancies. PD-1 and PD-L1 are expressed in tumor-infiltrating immune cells and most solid tumors, and they are closely associated with tumor development and prognosis ( 206 – 209 ). PD-L1-positive patients have a significantly lower 5-year survival rate than patients with non-PD-L1-positive tumors, and PD-L1 expression is an independent prognostic indicator ( 210 ).…”

Section: Pd-1/pd-l1 and Inhibitors In Human Hematological Malignanciesmentioning

confidence: 99%

The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers

et al. 2022

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Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, the natural receptor for PD-1, is mainly expressed in tumor cells. Studies have indicated that PD-1 and PD-L1 are closely associated with the progression of human cancers and are promising biomarkers for cancer therapy. Moreover, the interaction of PD-1 and PD-L1 is one of the important mechanism by which human tumors generate immune escape. This article provides a review on the role of PD-L1/PD-1, mechanisms of immune response and resistance, as well as immune-related adverse events in the treatment of anti-PD-1/PD-L1 immunotherapy in human cancers. Moreover, we summarized a large number of clinical trials to successfully reveal that PD-1/PD-L1 Immune-checkpoint inhibitors have manifested promising therapeutic effects, which have been evaluated from different perspectives, including overall survival, objective effective rate and medium progression-free survival. Finally, we pointed out the current problems faced by PD-1/PD-L1 Immune-checkpoint inhibitors and its future prospects. Although PD-1/PD-L1 immune checkpoint inhibitors have been widely used in the treatment of human cancers, tough challenges still remain. Combination therapy and predictive models based on integrated biomarker determination theory may be the future directions for the application of PD-1/PD-L1 Immune-checkpoint inhibitors in treating human cancers.

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Evaluation of PD-1 and PD-L1 expression in canine urothelial carcinoma cell lines

Cited by 12 publications

References 34 publications

Role of the tumour microenvironment in bladder cancer pathogenesis and value of the reverse translational approach: a tale of two species

Role of the tumour microenvironment in bladder cancer pathogenesis and value of the reverse translational approach: a tale of two species

Development of Monoclonal Antibodies Targeting Canine PD-L1 and PD-1 and Their Clinical Relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma

The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers

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