The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy

AbstractCheckpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells. Mocetinostat upregulatedPD-L1 and antigen presentation genes including class I and II human leukocyte antigen (HLA) family members in a panel of NSCLC cell lines in vitro. Mocetinostat target gene promoters were occupied by a class I HDAC and exhibited increased active histone marks after mocetinostat treatment. Mocetinostat synergized with interferon γ (IFN-γ) in regulating class II transactivator (CIITA), a master regulator of class II HLA gene expression. In a syngeneic tumor model, mocetinostat decreased intratumoral T-regulatory cells (Tregs) and potentially myeloid-derived suppressor cell (MDSC) populations and increased intratumoral CD8+  populations. In ex vivo assays, patient-derived, mocetinostat-treated Tregs also showed significant down regulation of FOXP3 and HELIOS. The combination of mocetinostat and a murine PD-L1 a...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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This article summarizes the established and new options in additive systemic treatment and presents the current state of treatment. PMID: 31705281 [PubMed - as supplied by publisher]
Source: Der Chirurg - Category: Surgery Authors: Tags: Chirurg Source Type: research
Conclusion: Yu-Ping-Feng induced M1 macrophages polarization, and then activated CD4+ T lymphocytes, resulting in killing of LLC cells. Yu-Ping-Feng was a potent regulator of M1 macrophage polarization and might have a promising application in tumor immunotherapy.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Publication date: November 2019Source: Journal of Geriatric Oncology, Volume 10, Issue 6, Supplement 1Author(s): M.L. Wong, A.K. Smith, C. Miaskowski, V. Musinipally, H.J. Cohen, V. Lam, M. Mazor, C.J. Ursem, K. Loh, J.A. Cohen, D. Shumay, A.O. Levin, N. Dixit, J. Grandi, L.C. Walter
Source: Journal of Geriatric Oncology - Category: Cancer & Oncology Source Type: research
Contributors : P Vijayanand ; C H Ottensmeier ; Tilman Sanchez-Elsner ; Eva M Garrido-MartinSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTumour Associated Macrophages (TAMs) are considered as functionally inactive or re-shaped by the tumour into a pro-tumour M2 phenotype. There is lack of transcriptomic data of TAMs purified from human cancers. We performed transcriptomic analyses on TAMs isolated from human NSCLC in comparison with matched tumour-free lung tissue macrophages from the same patients. TAMs are essentially M2 activated, but in some patients TAMs also exhibit a strong ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
ConclusionThis pilot study showed that MSAF could be another good indicator of therapeutic response, and clonal analysis could be clinically useful in monitoring clonal dynamics and detecting remote metastasis and early relapse.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Condition:   Carcinoma, Non-small Cell Lung Interventions:   Biological: nivolumab;   Biological: ipilimumab;   Drug: cabozantinib;   Drug: docetaxel;   Biological: ramucirumab;   Drug: lucitanib Sponsor:   Bristol-Myers Squibb Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Metastatic Lung Non-Small Cell Carcinoma;   Recurrent Lung Non-Small Cell Carcinoma;   Stage IV Lung Cancer AJCC v8;   Stage IVA Lung Cancer AJCC v8;   Stage IVB Lung Cancer AJCC v8 Interventions:   Procedure: Positron Emission Tomography;   Procedure: Computed Tomography;   Drug: Chemotherapy;   Biological: Immunotherapy;   Radiation: Radiation Therapy Sponsors:   University of Washingto...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Carcinoma, Non-small Cell Lung Interventions:   Biological: nivolumab;   Biological: ipilimumab;   Drug: cabozantinib;   Drug: docetaxel;   Biological: ramucirumab;   Drug: lucitanib Sponsor:   Bristol-Myers Squibb Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Metastatic Lung Non-Small Cell Carcinoma;   Recurrent Lung Non-Small Cell Carcinoma;   Stage IV Lung Cancer AJCC v8;   Stage IVA Lung Cancer AJCC v8;   Stage IVB Lung Cancer AJCC v8 Interventions:   Procedure: Positron Emission Tomography;   Procedure: Computed Tomography;   Drug: Chemotherapy;   Biological: Immunotherapy;   Radiation: Radiation Therapy Sponsors:   University of Washingto...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Carcinoma, Non-small Cell Lung Interventions:   Biological: nivolumab;   Biological: ipilimumab;   Drug: cabozantinib;   Drug: docetaxel;   Biological: ramucirumab;   Drug: lucitanib Sponsor:   Bristol-Myers Squibb Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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