Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is the seventh most prevalent cancer worldwide. Despite intensive treatments, the prognosis is unfavorable. Recently, immunotherapy has emerged as a novel therapeutic strategy, and several immune-checkpoint blockade blockers provide clinical benefits to patients. However, the response rates of these antibodies are limited, and there is a pressing need to increase the efficacy of immunotherapy for HNSCC patients. Epigenetic treatment is emerging as a promising combination approach able to change immune-related gene signatures in tumors and potentially increase the efficacy of immunotherapy. In this study, we sought to elucidate further immune-related gene signatures altered through epigenetic treatment and explored whether epigenetic drugs can increase the efficacy of anti PD-L1 treatment in HNSCC. Methods: At first, we treated six HNSCC cell lines with 5-azacytidine and romidepsin and analyzed gene expression patterns by microarray and TaqMan arrays analysis. We then explored the therapeutic efficacy of epigenetic treatment with an anti PD-L1 antibody in a syngeneic mouse model. Results: Our microarray analysis revealed the differential expression of immune-related genes in cell lines treated with epigenetic drugs, as compared to untreated controls. Most importantly, these array analyses showed a significant change in the transcription of some immune related-and biologically relevant genes, such as HLA-DRA, HMOX1, IFI6, IL12A, IRF7, NFKB2, RPL3L, STAT1, STAT3, CSF1, CSF2, FAS, OASL, and PD-L1, after epigenetic treatment. Furthermore, the combination of epigenetic treatment with an anti PD-L1 antibody significantly suppressed tumor growth in a syngeneic mouse model. In vivo tumors treated with epigenetic drugs expressed higher STAT1, STAT3, and PD-L1 compared to untreated tumors. Increased PD-L1 expression is postulated to increase the efficacy of anti PD-L1 treatment. Conclusions: Our results highlight the importance of a combinational strategy employing both epigenetic and immunotherapy in HNSCC.
背景/目的：头颈部鳞状细胞癌（HNSCC）是全球第七大常见癌症。尽管采取了强化治疗，其预后仍不理想。近年来，免疫疗法作为一种新型治疗策略崭露头角，多种免疫检查点阻断剂为患者带来了临床获益。然而，这些抗体的应答率有限，因此迫切需要提高HNSCC患者免疫治疗的疗效。表观遗传治疗正成为一种有前景的联合治疗手段，能够改变肿瘤中免疫相关基因的表达特征，并可能增强免疫治疗的疗效。本研究旨在进一步阐明表观遗传治疗所改变的免疫相关基因特征，并探讨表观遗传药物是否能增强抗PD-L1治疗在HNSCC中的疗效。方法：首先，我们使用5-氮杂胞苷和罗米地辛处理六种HNSCC细胞系，并通过微阵列和TaqMan阵列分析基因表达模式。随后，我们在同系小鼠模型中探索了表观遗传治疗联合抗PD-L1抗体的疗效。结果：微阵列分析显示，与未处理的对照组相比，经表观遗传药物处理的细胞系中免疫相关基因的表达存在差异。最重要的是，这些阵列分析表明，表观遗传治疗后，一些免疫相关且具有生物学意义的基因（如HLA-DRA、HMOX1、IFI6、IL12A、IRF7、NFKB2、RPL3L、STAT1、STAT3、CSF1、CSF2、FAS、OASL和PD-L1）的转录发生了显著变化。此外，在同系小鼠模型中，表观遗传治疗联合抗PD-L1抗体显著抑制了肿瘤生长。与未处理的肿瘤相比，经表观遗传药物处理的体内肿瘤表达了更高的STAT1、STAT3和PD-L1。PD-L1表达的增加被认为可增强抗PD-L1治疗的疗效。结论：我们的研究结果强调了在HNSCC中采用表观遗传治疗与免疫治疗联合策略的重要性。
肿瘤(癌症)患者之家