IL-27, a pleiotropic cytokine for fine-tuning the immune response in cancer

Beizavi, Zahra; Zohouri, Mahshid; Asadipour, Morvarid; Ghaderi, Abbas

doi:10.1080/08830185.2020.1840565

Cited by 28 publications

(15 citation statements)

References 102 publications

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“… 46 , 47 IL-27 had double ways in antitumor efficacy. 48 Both IL-15 and IL-27 contribute to maintain homeostasis of memory T cells. 49 , 50 As far, their association with survival in checkpoint blockade with or without conventional anti-tumor therapies was little known.…”

Section: Discussionmentioning

confidence: 99%

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study

et al. 2021

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Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m 2 ] plus docetaxel [25 mg/m 2 ] for 4 weeks) and radiotherapy (2.0 Gy/fraction, total 60 Gy) with camrelizumab (200 mg every 2 weeks for 32 weeks). Primary endpoints were safety and tolerability, and health-related quality of life. Secondary endpoints were radiological and pathological response rates, overall survival (OS), and progression-free survival (PFS). Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 40 Gy radiation. Twenty patients were enrolled. The most common treatment-related grade 3 adverse events included radiation esophagitis (20%) and esophageal fistula (10%). Serious treatment-related adverse events occurred in eight (40%) patients. No treatment-related deaths were reported. Health-related quality of life did not deteriorate. Thirteen (65%) patients had an objective response after 40 Gy radiation. At a median follow-up of 23.7 months (95% CI 21.9–24.5), OS and PFS time ranged from 8.2–28.5 and 4.0–28.5 months, respectively. The 12-month and 24-month OS rate was 85.0% and 69.6%; PFS rate was 80.0% and 65.0%. Tumor PD-L1 expression and CD11c + dendritic cells and peripheral-blood IL-27, IL-15, Eotaxin-3, and IL-22 were associated with OS. First-line concurrent chemoradiotherapy plus camrelizumab had a manageable safety profile and promising antitumour efficacy for ESCC, and deserves further study.

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Section: Discussionmentioning

confidence: 99%

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study

et al. 2021

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“…In addition, IL-27 can improve DC-mediated antigen presentation and result in Treg depletion ( 35 , 99 ). However, IL-27 has been identified as a pleiotropic cytokine ( 32 ) with the capacity to also activate Tregs ( 100 ) and induce immunosuppression through DCs ( 101 , 102 ), which may depend on their maturation state ( 103 ). In this study, we tested two different doses of rmIL-27 to determine the effects of IL-27 in our DTCVs.…”

Section: Discussionmentioning

confidence: 99%

“…IL-27, a cytokine belonging to the IL-12 family of cytokines, has been identified as a potential cancer vaccine adjuvant ( 31 ). IL-27 can signal in T cells, macrophages, and monocytes while also directly impacting cancer cell death and proliferation ( 32 , 33 ). Although IL-27 has been associated with both pro- and anti-tumor effects ( 34 ), elevated levels of IL-27 have demonstrated success in reducing cancer progression ( 31 , 35 ).…”

Section: Introductionmentioning

confidence: 99%

IL-27 Improves Prophylactic Protection Provided by a Dead Tumor Cell Vaccine in a Mouse Melanoma Model

et al. 2022

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The protocol used to induce cell death for generating vaccines from whole tumor cells is a critical consideration that impacts vaccine efficacy. Here we compared how different protocols used to induce cell death impacted protection provided by a prophylactic whole tumor cell vaccine in a mouse melanoma model. We found that melanoma cells exposed to γ-irradiation or lysis combined with UV-irradiation (LyUV) provided better protection against tumor challenge than lysis only or cells exposed to UV-irradiation. Furthermore, we found that the immunoregulatory cytokine, IL-27 enhanced protection against tumor growth in a dose-dependent manner when combined with either LyUV or γ-irradiated whole tumor cell vaccine preparations. Taken together, this data supports the use of LyUV as a potential protocol for developing whole tumor cell prophylactic cancer vaccines. We also showed that IL-27 can be used at low doses as a potent adjuvant in combination with LyUV or γ-irradiation treated cancer cells to improve the protection provided by a prophylactic cancer vaccine in a mouse melanoma model.

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“…The high predictive value of the eight-gene model for stage III and IV may suggests these genes, rather than acting as oncogenic drivers, are more critical in the progression and metastasis of OC. Among the genes in the model, HECT And RLD domain containing E3 ubiquitin protein ligase family member 1 (HERC1) (15), interleukin 27 receptor subunit alpha (IL27RA) (16), coiled-coil domain containing 80 (CCDC80) (17), and high mobility group box 3 (HMGB3) (18) may act as tumor suppressors or oncogenes in specific cancer types, while C-X-C motif chemokine 9 (CXCL9), C-X-C motif chemokine 11 (CXCL11), and peptidase inhibitor 3 (PI3) are closely related to OS in OC.…”

Section: Eight-gene Prognostic Modelmentioning

confidence: 99%

NOTCH2NLA silencing inhibits ovarian carcinoma progression and oncogenic activity in vivo and in vitro

Guo¹,

Sun²,

Zhao³

et al. 2021

Ann Transl Med

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IL-27, a pleiotropic cytokine for fine-tuning the immune response in cancer

Cited by 28 publications

References 102 publications

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study

IL-27 Improves Prophylactic Protection Provided by a Dead Tumor Cell Vaccine in a Mouse Melanoma Model

NOTCH2NLA silencing inhibits ovarian carcinoma progression and oncogenic activity in vivo and in vitro

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