Adenosine augments the production of IL-10 in cervical cancer cells through interaction with the A2B adenosine receptor, resulting in protection against the activity of cytotoxic T cells

Torres-Pineda, Daniela Berenice; Mora‐García, María de Lourdes; García‐Rocha, Rosario; Hernández‐Montes, Jorge; Weiss‐Steider, Benny; Montesinos-Montesinos, Juan José; Don‐López, Christian Azucena; Marín-Aquino, Luis Antonio; Muñóz-Godínez, Ricardo; Ibarra, Luis Roberto Ávila; López-Romero, Ricardo; Monroy-Garcı́a, Alberto

doi:10.1016/j.cyto.2020.155082

Cited by 8 publications

(7 citation statements)

References 41 publications

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“…It should be noted that a reduction in the level of class I HLAs facilitates the immune evasion of tumor cells [ 62 ]. Generally, it seems that in the case of cervical cancer, dampening IL-10 would help the proliferation of more CTLs in the tumor microenvironment and thereby enhancement of tumor regression [ 14 ]. In this study, it was observed that IL-10 blockade could increase the capacity of our adjuvant E7&IL-24 vaccine in eradicating tumor cells, which was further proved by an increase in the level of IFN-γ and caspase-9.…”

Section: Discussionmentioning

confidence: 99%

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Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Miri

Pourhossein

Hosseini

et al. 2022

Virol J

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Background MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. Methods For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. Results A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. Conclusion The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines’ low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies.

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Section: Discussionmentioning

confidence: 99%

“…Furthermore, owing to the role of IL-10 cytokine in the progression of HPV-positive cervical cancer cells [ 14 ], we assessed if the IL-10 blockade improved the efficacy of the E7&IL-24 candidate vaccine against TC-1 tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Miri

Pourhossein

Hosseini

et al. 2022

Virol J

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“…Zhao et al, in a meta-analysis, verified the impact of IL-10 on outcome in several tumors, indicating that elevated serum levels of IL-10 have correlated with poor prognosis and low survival, suggesting that this comprises a promising biomarker in the evaluation of progression tumor and survival time in solid and hematological tumors [ 41 ]. Torres-Pineda et al reported that cervical cancer cells produce high concentrations of Ado and increased levels of IL-10, promoting immune evasion and tumor progression [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Deregulation of purinergic ectoenzyme activity in head and neck cancer promotes immunosuppression

et al. 2022

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Background Head and neck cancer (HNC) comprises a spectrum of neoplasms that affect the upper aerodigestive tract and are the sixth most common cancers worldwide. Individuals with HNC exhibit various symptoms and metabolic changes, including immune alterations and alterations of the purinergic pathway, which may signal worse outcomes. Therefore, the purpose of this research was to measure the activity of purinergic ectoenzymes and interleukins in patients with HNC, oral cavity cancer, and larynx cancer. Methods and Results We recruited 32 patients and 33 healthy control subjects and performed the laboratory analyses. We identified dysregulation in the purinergic signaling pathway characterized by an increase in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and a decrease in the deamination of adenosine to inosine in these cancers (p < 0.05). These alterations were likely caused by increased activity of the ectoenzymes E-NTPDase and ecto-5’-nucleotidase and reduced adenosine deaminase activity. This dysregulation was associated with immune alterations, increased levels of IL-10, and decreased myeloperoxidase activity (p < 0.05), suggesting immunosuppression in these patients and suggesting possible accumulation of adenosine in the extracellular environment. Conclusions Adenosine is a potent immunosuppressive molecule associated with tumor progression and immune evasion. Our findings suggest a relationship between extracellular purines and the development and progression of the tumor microenvironment and poor outcomes. These findings increase the understanding of biological mechanisms related to HNC and demonstrate that these components are potential diagnostic markers and therapeutic targets for future management strategies and improvement in the quality of life.

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“…[ 13 ] IL-6 and IL-10 have been implicated in the development of HPV-induced cervical lesions and inhibition of immune cells, which are important for viral elimination. [ 14 ] The immunoregulatory cytokine IL-10 decreases the expression of histocompatibility complex class I molecules in cervical cancer cells [ 10 , 15 ] and protects against the cytotoxic activity of cytotoxic T lymphocytes. [ 15 ] purinergic ligand-gated ion channel 7 and adenosine A(2A) receptors are considered novel therapeutic targets because blocking purinergic ligand-gated ion channel 7 results in reduced release of proinflammatory cytokines, whereas blocking adenosine A(2A) increases the activation of cytotoxic T lymphocytes to fight cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

A bibliometric analysis of global research trends of inflammation in cervical cancer: A review

Kang,

Qiu,

Wei

et al. 2023

Medicine

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Cervical cancer is a common malignant tumor and a leading cause of death in women worldwide. It plays a crucial role in tumorigenesis and progression of cervical cancer. A total of 1606 references on inflammation in cervical cancer were retrieved from the Web of Science Core Collection and visual analysis was performed using VOSviewer. Inflammation in cervical cancer has attracted the attention of researchers. Even though China is the country that publishes the most papers, with the most of the top-ranking institutions, there is no extensive collaboration and exchange of papers by Chinese scholars. PLOS One is a popular journal on inflammation in cervical cancer. Instead, authors from other countries perform better, for example, the Sjoerd H. Van Der Burg is the most widely cited author and “M2 macrophages induced by prostaglandin E2 and IL-6 from cervical carcinoma are switched to activated M1 macrophages by CD4 + Th1 cells” (Moniek Heusinkveld, Leiden University Medical Center) is the most cited article of inflammation in cervical cancer. Keywords associated with “apoptosis,” “HPV,” “NF-κB,” and “oxidative stress have been used in many studies, and keywords associated with “apoptosis,” “human papillomavirus (HPV),” “NF-κB,” and “oxidative stress” are involved in many studies, and there may be more research ideas in the future. From the perspective of precision medicine, more substantive research articles can promote scientific value, strengthen communication and cooperation, produce more extensive research results, and greatly promote the clinical diagnosis and treatment of cervical cancer. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Adenosine augments the production of IL-10 in cervical cancer cells through interaction with the A2B adenosine receptor, resulting in protection against the activity of cytotoxic T cells

Cited by 8 publications

References 41 publications

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Enhanced synergistic antitumor effect of a DNA vaccine with anticancer cytokine, MDA-7/IL-24, and immune checkpoint blockade

Deregulation of purinergic ectoenzyme activity in head and neck cancer promotes immunosuppression

A bibliometric analysis of global research trends of inflammation in cervical cancer: A review

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