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HDAC抑制用于优化NY-ESO-1阳性软组织肉瘤的细胞免疫治疗

HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma.

作者信息

Gong Wenjie, Wang Lei, Schubert Maria-Luisa, Kleist Christian, Neuber Brigitte, Wang Sanmei, Yang Mingya, Hückelhoven-Krauss Angela, Wu Depei, Schmitt Anita, Müller-Tidow Carsten, Shiku Hiroshi, Schmitt Michael, Sellner Leopold

机构信息

Department of Internal Medicine V, Heidelberg University Hospital, 69120 Heidelberg, Germany.

Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou 215005, China.

出版信息

Biomedicines. 2022 Feb 3;10(2):373. doi: 10.3390/biomedicines10020373.

DOI:10.3390/biomedicines10020373
PMID:35203582
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8962361/
Abstract

Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-testis antigen NY-ESO-1 using histone deacetylase inhibitors (HDACis). In this study, the ex vivo effect of combining NY-ESO-1-specific T cells with the clinically approved pan HDACis panobinostat or vorionstat was investigated. Our data demonstrated that STS cells were sensitive to HDACis. Administration of HDACi prior to NY-ESO-1-specific T cells exerted enhanced lysis against the NY-ESO-1+ STS cell line SW982. This correlated with an increase in the NY-ESO-1 and HLA-ABC expression of SW982 cells, as well as increased CD25 expression on NY-ESO-1-specific T cells. Furthermore, the immune reactivity of NY-ESO-1-specific CD8+ T cells in terms of cytokine release was enhanced by HDACis. In summary, pretreatment with HDACis represents a potential means of enhancing the cytotoxic efficacy of NY-ESO-1-specific T cells against NY-ESO-1-positive STS.

摘要

采用NY-ESO-1特异性T细胞进行过继性细胞治疗是治疗软组织肉瘤（STS）的一种有前景的选择，但在大多数情况下只能实现短暂的肿瘤控制。一种优化这种细胞治疗方法的策略可能是使用组蛋白去乙酰化酶抑制剂（HDACi）调节癌胚抗原NY-ESO-1的表达。在本研究中，研究了将NY-ESO-1特异性T细胞与临床批准的泛HDACi帕比司他或伏立诺他联合使用的体外效果。我们的数据表明，STS细胞对HDACi敏感。在NY-ESO-1特异性T细胞之前给予HDACi可增强对NY-ESO-1+ STS细胞系SW982的杀伤作用。这与SW982细胞中NY-ESO-1和HLA-ABC表达的增加以及NY-ESO-1特异性T细胞上CD25表达的增加相关。此外，HDACi增强了NY-ESO-1特异性CD8+ T细胞在细胞因子释放方面的免疫反应性。总之，HDACi预处理是增强NY-ESO-1特异性T细胞对NY-ESO-1阳性STS细胞毒性作用的一种潜在手段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/3621d43c0029/biomedicines-10-00373-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/c4f4a71aa508/biomedicines-10-00373-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/00656779f272/biomedicines-10-00373-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/3ebb0abb4899/biomedicines-10-00373-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/3621d43c0029/biomedicines-10-00373-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/c4f4a71aa508/biomedicines-10-00373-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/c742f1197911/biomedicines-10-00373-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/00656779f272/biomedicines-10-00373-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/41d3e111db5b/biomedicines-10-00373-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/3ebb0abb4899/biomedicines-10-00373-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a858/8962361/3621d43c0029/biomedicines-10-00373-g006.jpg

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