Author Correction: Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells

Knox, Tessa; Sahakian, Eva; Banik, Debarati; Hadley, Melissa; Palmer, Erica; Noonepalle, Satish; Kim, Jennifer; Powers, John J.; Gracia-Hernandez, Maria; Oliveira, Vasco; Cheng, Fengdong; Chen, Jie; Bařinka, Cyril; Pinilla‐Ibarz, Javier; Lee, Norman H.; Kozikowski, Alan P.; Villagra, Alejandro

doi:10.1038/s41598-019-51403-6

Cited by 58 publications

(5 citation statements)

References 56 publications

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“…In another study, the HDAC6 inhibitor nexturastat A reduced PD-L1 expression provoked by anti-PD1 treatment and subsequently depleted protumorigenic M2 macrophages. In combination with PD1 blockade, it increased the total number of tumor infiltrating CD8+ lymphocytes [182]. In contrast, in primary melanoma cells, class I-selective HDACis dosedependently increased PD-L1 expression.…”

Section: Immune Effectsmentioning

confidence: 95%

Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives

Jenke

Reßing

Hansen

et al. 2021

Cancers

107

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The increasing knowledge of molecular drivers of tumorigenesis has fueled targeted cancer therapies based on specific inhibitors. Beyond “classic” oncogene inhibitors, epigenetic therapy is an emerging field. Epigenetic alterations can occur at any time during cancer progression, altering the structure of the chromatin, the accessibility for transcription factors and thus the transcription of genes. They rely on post-translational histone modifications, particularly the acetylation of histone lysine residues, and are determined by the inverse action of histone acetyltransferases (HATs) and histone deacetylases (HDACs). Importantly, HDACs are often aberrantly overexpressed, predominantly leading to the transcriptional repression of tumor suppressor genes. Thus, histone deacetylase inhibitors (HDACis) are powerful drugs, with some already approved for certain hematological cancers. Albeit HDACis show activity in solid tumors as well, further refinement and the development of novel drugs are needed. This review describes the capability of HDACis to influence various pathways and, based on this knowledge, gives a comprehensive overview of various preclinical and clinical studies on solid tumors. A particular focus is placed on strategies for achieving higher efficacy by combination therapies, including phosphoinositide 3-kinase (PI3K)-EGFR inhibitors and hormone- or immunotherapy. This also includes new bifunctional inhibitors as well as novel approaches for HDAC degradation via PROteolysis-TArgeting Chimeras (PROTACs).

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Section: Immune Effectsmentioning

confidence: 95%

Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives

Jenke

Reßing

Hansen

et al. 2021

Cancers

107

View full text Add to dashboard Cite

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“…On the one hand, it enhances the antitumor ability of immune cells by enhancing the intratumoral infiltration of CD8 + T cells and macrophages, upregulating costimulatory molecules, promoting tumor-specific T cell-mediated cancer cell killing and sensitizing tumor cells to NK cell lysis. On the other hand, it inhibits intratumoral infiltration of myeloid-derived suppressor cells (MDSCs), primary M2 macrophages and T-regulatory cells[ 23 - 25 ]. HDACis may also enhance checkpoint inhibitor therapy.…”

Section: Discussionmentioning

confidence: 99%

Chidamide and sintilimab combination in diffuse large B-cell lymphoma progressing after chimeric antigen receptor T therapy

Hao¹,

Chen²,

Yuan³

et al. 2022

WJCC

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BACKGROUND Diffuse large B-cell lymphoma (DLBCL) is curable with first-line chemoimmunotherapy but patients with relapsed/refractory (R/R) DLBCL still face a poor prognosis. For patients with R/R DLBCL, the complete response rate to traditional next-line therapy is only 7% and the median overall survival is 6.3 mo. Recently, CD19-targeting chimeric antigen receptor T cells (CAR-T) have shown promise in clinical trials. However, approximately 50% of patients treated with CAR-T cells ultimately progress and few salvage therapies are effective. CASE SUMMARY Here, we report on 7 patients with R/R DLBCL whose disease progressed after CAR-T infusion. They received a PD-1 inhibitor (sintilimab) and a histone deacetylase inhibitor (chidamide). Five of the 7 patients tolerated the treatment without any serious adverse events. Two patients discontinued the treatment due to lung infection and rash. At the 20-mo follow-up, the median overall survival of these 7 patients was 6 mo. Of note, there were 2 complete response rates (CRs) and 2 partial response rates (PRs) during this novel therapy, with an overall response rate (ORR) of 57.1%, and one patient had a durable CR that lasted at least 20 mo. CONCLUSION In conclusion, chidamide combined with sintilimab may be a choice for DLBCL patients progressing after CD19-targeting CAR-T therapy.

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“…At present, only a few HDACis, such as vorinostat, romidepsin, belinostat and Panobinostat, have been approved by the FDA to treat malignancies, while other HDACis are undergoing various clinical trials as options for the treatment of malignancies (69). HDACis exert antitumor effects by inducing cell apoptosis, inhibiting angiogenesis, and regulating cell autophagy and immune responses; however, to the best of our knowledge, the mechanisms by which they regulate PD-L1 have not been well defined (70,71).…”

Section: Regulation Of Pd-l1 Expression In Solid Tumors By Histone Ac...mentioning

confidence: 99%

Epigenetic modifications: Critical participants of the PD‑L1 regulatory mechanism in solid tumors (Review)

Wang

et al. 2022

Int J Oncol

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Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis have achieved marked and durable efficacy in patients with different solid tumors and have improved their survival. However, the presence of primary or acquired resistance to immune checkpoint blockades results in only a small fraction of patients benefiting from the treatment. An increasing number of preclinical studies have reported that PD-L1 expression in tumor cells is involved in a number of epigenetic changes, including histone modifications, non-coding RNA regulation and DNA methylation. In addition, multiple epigenetic targeting drugs have been demonstrated to directly or indirectly interfere with PD-L1 expression in various cancer models. This provides opportunities to better characterize the regulatory mechanisms of PD-L1 expression and explore novel therapeutic strategies to improve immunosuppressant response rates and overcome drug resistance. The present review focuses on the latest findings and evidence on the epigenetic mechanism regulating PD-L1 expression and discusses the biological and clinical implications of this regulatory mechanism in solid tumors. A rational combination of epigenetic regulation and PD-1/PD-L1 axis blockade may improve the prognosis of patients with solid tumors.

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Author Correction: Selective HDAC6 inhibitors improve anti-PD-1 immune checkpoint blockade therapy by decreasing the anti-inflammatory phenotype of macrophages and down-regulation of immunosuppressive proteins in tumor cells

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cited by 58 publications

References 56 publications

Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives

Anticancer Therapy with HDAC Inhibitors: Mechanism-Based Combination Strategies and Future Perspectives

Chidamide and sintilimab combination in diffuse large B-cell lymphoma progressing after chimeric antigen receptor T therapy

Epigenetic modifications: Critical participants of the PD‑L1 regulatory mechanism in solid tumors (Review)

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