Cytokine-based Cancer Immunotherapy: Challenges and Opportunities for IL-10

Rallis, Kathrine S; Corrigan, Amber E; Dadah, Hashim; George, Alan Mathew; Keshwara, Sumirat M; Sideris, Michail; Szabados, Bernadett

doi:10.21873/anticanres.15110

Cited by 58 publications

(36 citation statements)

References 60 publications

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“…IL-10 plays a pleomorphic role in cancer immunity [93]. It has been classically considered an immunosuppressive factor that promotes tumor growth, while recent studies showed exogenous IL-10 administration can induce anti-tumor effects by promoting CD8 T cell-mediated anti-tumor immunity [94,95].…”

Section: Il-10mentioning

confidence: 99%

Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors

Chon

Kim

2021

IJMS

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As cancer immunotherapy using immune checkpoint inhibitors (ICIs) is rapidly evolving in clinical practice, it is necessary to identify biomarkers that will allow the selection of cancer patients who will benefit most or least from ICIs and to longitudinally monitor patients′ immune responses during treatment. Various peripheral blood-based immune biomarkers are being identified with recent advances in high-throughput multiplexed analytical technologies. The identification of these biomarkers, which can be easily detected in blood samples using non-invasive and repeatable methods, will contribute to overcoming the limitations of previously used tissue-based biomarkers. Here, we discuss the potential of circulating immune cells, soluble immune and inflammatory molecules, circulating tumor cells and DNA, exosomes, and the blood-based tumor mutational burden, as biomarkers for the prediction of immune responses and clinical benefit from ICI treatment in patients with advanced cancer.

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Section: Il-10mentioning

confidence: 99%

Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors

Chon

Kim

2021

IJMS

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“…IL-10 induced Fas/FasL pathway is important for disease control and has otherwise been an under reported functional mechanism of IL-10 signaling ( Figure 1 ) ( 50 – 52 ). Similarly, IL-10 has also been shown to induce the production of cytotoxic enzymes and IFNγ in CD8 + T-cells, and, in conjunction with IL-2, differentiation of cytotoxic T-cells from their precursors, demonstrating a dual function of IL-10 signaling in immune regulation ( 53 , 54 ).…”

Section: Introductionmentioning

confidence: 99%

Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

et al. 2022

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Regulatory T-cells (Treg) are critical for the maintenance of immune homeostasis and tolerance induction. While the immunosuppressive mechanisms of Treg have been extensively investigated for decades, the mechanisms responsible for Treg cytotoxicity and their therapeutic potential in regulating immune responses have been incompletely explored and exploited. Conventional cytotoxic T effector cells (Teffs) are known to be important for adaptive immune responses, particularly in the settings of viral infections and cancer. CD4+ and CD8+ Treg subsets may also share similar cytotoxic properties with conventional Teffs. Cytotoxic effector Treg (cyTreg) are a heterogeneous population in the periphery that retain the capacity to suppress T-cell proliferation and activation, induce cellular apoptosis, and migrate to tissues to ensure immune homeostasis. The latter can occur through several cytolytic mechanisms, including the Granzyme/Perforin and Fas/FasL signaling pathways. This review focuses on the current knowledge and recent advances in our understanding of cyTreg and their potential application in the treatment of human disease, particularly Graft-versus-Host Disease (GVHD).

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“…A total of 44/70 immunomodulators in the TCGA-LUAD cohort and 57/70 immunomodulators in the TCGA-LUSC cohort presented significant correlation with the transcript level of IFI44L . As reported, the immunomodulators have tremendous and abundant functions in the TME, as well as tumor development and progression ( 35 , 36 ). Among these immunomodulators, there are considerable proportions of tumor necrosis factor (TNF) and its receptor (TNFR); as the term suggest, they belong to the tumor necrosis factor super family (TNFSF) and tumor necrosis factor receptor super family (TNFRSF).…”

Section: Discussionmentioning

confidence: 95%

Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer

et al. 2022

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Interferon-induced protein 44-like (IFI44L), a type I interferon-stimulated gene (ISG), has been reported to be involved in innate immune processes and to act as a tumor suppressor in several cancers. However, its immune implication on lung cancer remains unclear. Here, we systemically analyzed the immune association of IFI44L with multiple tumor-infiltrating immune cells (TIICs) and immunomodulators through bioinformatics methods in The Cancer Genome Atlas (TCGA) lung cancer cohorts. Then, the IFI44L-related immunomodulators were selected to construct the prognostic signatures in the lung adenocarcinoma (LUAD) cohort and the lung squamous cell carcinoma (LUSC) cohort, respectively. Concordance index and time-dependent receiver operating characteristics (ROC) curves were applied to evaluate the prognostic signatures. GSE72094 and GSE50081 were used to validate the TCGA-LUAD signature and TCGA-LUSC signature, respectively. A nomogram was established by risk score and clinical features in the LUAD cohort. Finally, the prognostic value and biological function of IFI44L were verified in a real-world cohort and in vitro experiments. The results indicated that IFI44L showed significant correlation with TIICs in LUAD and LUSC samples. Functional enrichment analysis showed that IFI44L may participate in various cancer/immune-related pathways, including JAK/STAT signaling pathway and NF-κB signaling pathway. A total of 44 immunomodulators presented obvious association with IFI44L in the TCGA-LUAD cohort and a robust 10-immunomodulator signature was constructed. Patients in the higher-risk group presented worse prognosis than those in the lower-risk group. Notably, the risk signature was successfully validated in GSE72094. Multivariate Cox regression suggested that the risk signature could act as independent prognostic factors in both TCGA-LUAD and GSE72094 cohorts. Besides, a 17-immunomodulator signature was established in the TCGA-LUSC cohort and similar results were presented through analysis. The nomogram exhibited good accuracy in predicting overall survival (OS) outcome among TCGA-LUAD patients than the risk signature and other clinical features, with the area under curve values being 0.782 at 1 year, 0.825 at 3 years, and 0.792 at 5 years. Finally, tissue microarray analysis indicated that higher expression of IFI44L presented opposite relationship with pathological stage (p = 0.016) and a better outcome among lung cancer patients (p = 0.024). Functional experiments found that IFI44L overexpression significantly inhibited the proliferation, migration, and invasion in LUAD and LUSC cells; RT-qPCR experiments verified the correlation between the expression level of IFI44L with multiple immunomodulators in SPC-A-1 and NCI-H520 cells. In conclusion, our research highlighted that IFI44L is associated with tumor immune infiltration and provided information on IFI44L’s immune implication, which indicates that IFI44L has potential clinical immunotherapeutic value and the proposed nomogram is a promising biomarker for non-small cell lung cancer patients.

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Cytokine-based Cancer Immunotherapy: Challenges and Opportunities for IL-10

Cited by 58 publications

References 60 publications

Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors

Peripheral Blood-Based Biomarkers for Immune Checkpoint Inhibitors

Cytolytic CD4+ and CD8+ Regulatory T-Cells and Implications for Developing Immunotherapies to Combat Graft-Versus-Host Disease

Comprehensive Analysis of Immune Implication and Prognostic Value of IFI44L in Non-Small Cell Lung Cancer

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