Role of the HDAC6/STAT3 pathway in regulating PD-L1 expression in osteosarcoma cell lines

Keremu, Ajimu; Aimaiti, Abudusaimi; Liang, Zhilin; Zou, Xiaoguang

doi:10.1007/s00280-018-3721-6

Cited by 41 publications

(38 citation statements)

References 40 publications

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“…For example, STAT3 increased CTLA-4 expression in tumor-associated B cells in a JAK-dependent manner [ 161 ] and enhanced CTLA-4 expression in Treg cells through IL-10 [ 162 ]. In addition, STAT3 mediated HDAC6-induced PD-L1 expression in osteosarcoma cells [ 163 ]. Conversely, recent evidence also suggests a role of immune checkpoint molecules in STAT3 expression.…”

Section: Integrating Stat3 In Combination Cancer Immunotherapymentioning

confidence: 99%

Targeting STAT3 in Cancer Immunotherapy

et al. 2020

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As a point of convergence for numerous oncogenic signaling pathways, signal transducer and activator of transcription 3 (STAT3) is central in regulating the anti-tumor immune response. STAT3 is broadly hyperactivated both in cancer and non-cancerous cells within the tumor ecosystem and plays important roles in inhibiting the expression of crucial immune activation regulators and promoting the production of immunosuppressive factors. Therefore, targeting the STAT3 signaling pathway has emerged as a promising therapeutic strategy for numerous cancers. In this review, we outline the importance of STAT3 signaling pathway in tumorigenesis and its immune regulation, and highlight the current status for the development of STAT3-targeting therapeutic approaches. We also summarize and discuss recent advances in STAT3-based combination immunotherapy in detail. These endeavors provide new insights into the translational application of STAT3 in cancer and may contribute to the promotion of more effective treatments toward malignancies.

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Section: Integrating Stat3 In Combination Cancer Immunotherapymentioning

confidence: 99%

Targeting STAT3 in Cancer Immunotherapy

et al. 2020

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“…In more recent work on melanoma, HDAC6 was also found to be regulating the expression of PD-L1 in a STAT3-dependent manner now established in multiple tumor types. While primarily observed in melanoma [182], this relationship is now also established in osteosarcoma [183] and chronic lymphocytic leukemia (CLL) [184]. This observation opened a novel avenue of combining HDAC6 inhibition with the immunotherapeutic modality of PD1/PDL1 pathway.…”

Section: Selective Hdacismentioning

confidence: 99%

Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy

Banik

Moufarrij

Villagra

2019

IJMS

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Long-standing efforts to identify the multifaceted roles of histone deacetylase inhibitors (HDACis) have positioned these agents as promising drug candidates in combatting cancer, autoimmune, neurodegenerative, and infectious diseases. The same has also encouraged the evaluation of multiple HDACi candidates in preclinical studies in cancer and other diseases as well as the FDA-approval towards clinical use for specific agents. In this review, we have discussed how the efficacy of immunotherapy can be leveraged by combining it with HDACis. We have also included a brief overview of the classification of HDACis as well as their various roles in physiological and pathophysiological scenarios to target key cellular processes promoting the initiation, establishment, and progression of cancer. Given the critical role of the tumor microenvironment (TME) towards the outcome of anticancer therapies, we have also discussed the effect of HDACis on different components of the TME. We then have gradually progressed into examples of specific pan-HDACis, class I HDACi, and selective HDACis that either have been incorporated into clinical trials or show promising preclinical effects for future consideration. Finally, we have included examples of ongoing trials for each of the above categories of HDACis as standalone agents or in combination with immunotherapeutic approaches.

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“…STAT3 has been demonstrated to bind to the Pdcd1l1 promoter (coding for PD-L1) to regulate its transcriptional expression in cancer cells. It requires either mutated oncogene chimeric nucleophosmin/anaplastic lymphoma kinase (ALK) in T-cell lymphoma [173], Latent membrane protein-1 (LMP1) of Epstein–Barr virus in nasopharyngeal carcinoma [174], HDAC6 in osteosarcoma [175], NF-κB in melanoma [176] or HIF-1α in pulmonary adenocarcinoma [177]. In contrast, a study shows that STAT3 is necessary for docetaxel-mediated inhibition of PD-1 expression [178].…”

Section: Stat3 and Check Points Inhibitorsmentioning

confidence: 99%

STAT3, a Master Regulator of Anti-Tumor Immune Response

Rébé

Ghiringhelli

2019

Cancers

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Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g., by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors.

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Role of the HDAC6/STAT3 pathway in regulating PD-L1 expression in osteosarcoma cell lines

Cited by 41 publications

References 40 publications

Targeting STAT3 in Cancer Immunotherapy

Targeting STAT3 in Cancer Immunotherapy

Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy

STAT3, a Master Regulator of Anti-Tumor Immune Response

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