<scp>PD</scp>‐L1 and <scp>IDO</scp> expression in cervical and vulvar invasive and intraepithelial squamous neoplasias: implications for combination immunotherapy

Chinn, Zachary; Stoler, Mark H.; Mills, Anne M.

doi:10.1111/his.13723

Cited by 46 publications

(48 citation statements)

References 75 publications

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“…This result is consistent with the finding of Sznurkowski et al that show 96.05% of VSCC mostly diffuse IDO expression in Poland population . However, two other studies have shown a lower IDO expression in the Netherlands population (50.4%) and in United States (30%) . This inconsistency may be because of the ethnicity and/or the used anti‐IDO antibody that is different in de Jong study (Monoclonal antibody, clone 10.1; Millipore, Chemicon), and in Chinn study (Polyclonal antibody, HPA 023072, Sigma Prestige).…”

Section: Discussionsupporting

confidence: 92%

“…50 However, two other studies have shown a lower IDO expression in the Netherlands population (50.4%) 4 and in United States (30%). 51 This inconsistency may be because of the ethnicity and/or the used anti-IDO antibody that is different in de Jong study (Monoclonal antibody, clone 10.1; Millipore, Chemicon), and in Chinn study (Polyclonal antibody, HPA 023072, Sigma Prestige). This increase of IDO might have effects on CTL and NK cells by the decrease of tryptophan level and the increase of kynurenine in the vulvar microenvironment, reducing their activation or inducing their apoptosis, and on LT regulators by their activation 16,21,52 (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

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HLA‐G, HLA‐E, and IDO overexpression predicts a worse survival of Tunisian patients with vulvar squamous cell carcinoma

Boujelbène

Yahia

Babay

et al. 2019

HLA

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Little is known about non‐classical HLA molecules in vulvar squamous cell carcinoma (VSCC). Because of the indoleamine‐2,3‐dioxygenase (IDO) immune tolerant role in association with HLA‐G, we evaluated the clinical and prognostic value of HLA‐G, HLA‐E, and IDO in VSCC. HLA‐G, HLA‐E, and IDO expression was determined by immunohistochemistry in VSCC and associated with clinicopathological parameters and disease outcome. These three molecules were highly represented in tumoral tissues vs healthy matched vulvar tissues (P = 0.0001). Significant differences in HLA‐G expression in stages, tumor size, tumor invasion depth, and resection margins subgroups were reported (P < 0.05). At 5 years, the cumulative survival rates was of 79.8% in patients with HLA‐Glow expression vs 12.5% in those with HLA‐Ghigh expression (P < 3 × 10−5). Similarly, patients with IDOhigh expression were at a significantly reduced overall survival (OS) and disease‐free survival (DFS) rates (P = 0.011 and 0.045, respectively). The overexpression of the three molecules together worsen survival rates of VSCC patients (OS: P = 0.000038, DFS: P = 0.000085). Altogether, our results showed that HLA‐G, HLA‐E, and IDO may represent novel candidate markers for patients' prognosis and potential targets for VSCC therapy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

HLA‐G, HLA‐E, and IDO overexpression predicts a worse survival of Tunisian patients with vulvar squamous cell carcinoma

Boujelbène

Yahia

Babay

et al. 2019

HLA

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“…IDO1 is known to induce immune suppression in local tumor environment by promoting the differentiation of regulatory T cell and inhibiting the function of effector T cells [19]. And IDO1 is commonly co-expressed with programmed death ligand 1(PD-L1) in cervical squamous carcinomas [20].…”

Section: Discussionmentioning

confidence: 99%

The IFN-γ-IDO1-Kynureine Pathway-Induced Autophagy in Cervical Cancer Cell Promotes Phagocytosis of Macrophage

Yang

Tan¹

Niu

et al. 2020

Preprint

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Bachground: Cervical cancer is a common malignant disease in female patients accompanied by active autophagy in tumor cells. However, much remains unknown about the regulatory factors of autophagy and its effect on immune response.Methods: Autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine, and epacadostat was detected by western blot and autophagy detection kit. After co-cultured with pre-treated HeLa and SiHa cells, U937 was detected by flow cytometry to analyze the CD80, CD86, CD163, CD206 expression and the phagocytosis. Results: IFN-γ could significantly increase the autophagy level of HeLa and SiHa cells by promoting the indoleamine-2,3-dioxygenase-1 (IDO1) expression. HeLa and SiHa cells treated with recombinant human IFN-γ could significantly increase the phagocytosis and CD80, CD86 expression of U937, and this effect was associated with the autophagy in tumor cells. IFN-γ treatment and IDO1 overexpression promote tryptophan depletion and kynurenine accumulation in cervical cancer cells, and the latter was proved to be more potent in inducing autophagy of cervical cancer cells and promoting phagocytosis of macrophage. In vivo, IDO1 overexpression could significantly restrict the tumor growth in C57 mice, and the phagocytosis of macrophage was enhanced.Conclusions: IFN-γ promotes the autophagy of cervical cancer cell possibly through IDO1 expression and kynurenine metabolism, and further promotes macrophage phagocytosis in cervical cancer.

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“…Vulvar cancer is one of the less frequently diagnosed gynecological cancers, with 6120 new cases predicted to be encountered in the US in 2020 and 1350 deaths expected due to this disease (Table 1) [1]. PD-L1 is reported to be expressed in most vulva squamous cell carcinoma [6,142,143], even though the significance of this parameter is not yet well understood. Clinical trials for vulvar and vaginal cancer are often part of basket studies of HPV-associated cancers (CheckMate 358).…”

Section: Cervical and Other Female Gynecologic Cancersmentioning

confidence: 99%

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Drakes

Czerlanis

Stiff

2020

Cancers

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This review provides an update on the current use of immune checkpoint inhibitors (ICI) in female gynecologic cancers, and it addresses the potential of these agents to provide therapy options for disease management and long-term remission in advanced disease patients, where surgery, chemotherapy, and/or radiation fail to meet this goal. The topic of immune checkpoint inhibitors (ICI) blocking cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the programmed death-1 (PD-1) axis has come to the forefront of translational medicine over the last decade for several malignancies. The text will focus primarily on a discussion of ovarian cancer, which is the most frequent cause of death of gynecologic cancers; endometrial cancer, which is the most often diagnosed gynecologic cancer; and cervical cancer, which is the third most common female gynecologic malignancy, all of which unfavorably alter the lives of many women. We will address the critical factors that regulate the outcome of these cancer types to ICI therapy, the ongoing clinical trials in this area, as well as the adverse immune responses that impact the outcome of patients given ICI regimens.

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PD‐L1 and IDO expression in cervical and vulvar invasive and intraepithelial squamous neoplasias: implications for combination immunotherapy

Cited by 46 publications

References 75 publications

HLA‐G, HLA‐E, and IDO overexpression predicts a worse survival of Tunisian patients with vulvar squamous cell carcinoma

HLA‐G, HLA‐E, and IDO overexpression predicts a worse survival of Tunisian patients with vulvar squamous cell carcinoma

The IFN-γ-IDO1-Kynureine Pathway-Induced Autophagy in Cervical Cancer Cell Promotes Phagocytosis of Macrophage

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

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