Noncoding Ribonucleic Acids (RNAs) May Improve Response to Immunotherapy in Pancreatic Cancer

IF 4.9 Q1 CHEMISTRY, MEDICINAL

ACS Pharmacology and Translational Science Pub Date : 2024-08-06 DOI:10.1021/acsptsci.3c0039410.1021/acsptsci.3c00394

Moein Ala*,

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引用次数: 0

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the seventh most common cause of cancer-related mortality. Despite different methods of treatment, nearly more than 90% of patients with PDAC die shortly after diagnosis. Contrary to promising results in other cancers, immune checkpoint inhibitors (ICIs) showed limited success in PDAC. Recent studies have shown that noncoding RNAs (ncRNAs) are extensively involved in PDAC cell–immune cell interaction and mediate immune evasion in this vicious cancer. PDAC cells recruit numerous ncRNAs to widely affect the phenotype and function of immune cells through various mechanisms. For instance, PDAC cells upregulate miR-301a and downregulate miR-340 to induce M2 polarization of macrophages or overexpress miR-203, miR-146a, and miR-212-3p to downregulate toll-like receptor 4 (TLR4), CD80, CD86, CD1a, major histocompatibility complex (MHC) II, and CD83, thereby evading recognition by dendritic cells. By downregulating miR-4299 and miR-153, PDAC cells can decrease the expression of NK group 2D (NKG2D) and MHC class I chain-related molecules A and B (MICA/B) to blunt the natural killer (NK) cell response. PDAC cells also highly express lncRNA AL137789.1, hsa_circ_0046523, lncRNA LINC00460, and miR-155-5p to upregulate immune checkpoint proteins and escape T cell cytotoxicity. On the other hand, ncRNAs derived from suppressive immune cells promote proliferation, invasion, and drug resistance in PDAC cells. ncRNAs can be applied to overcome resistance to ICIs, monitor the immune microenvironment of PDAC, and predict response to ICIs. This Review article comprehensively discusses recent findings regarding the roles of ncRNAs in the immune evasion of PDAC.

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非编码核糖核酸 (RNA) 可改善胰腺癌患者对免疫疗法的反应

胰腺导管腺癌（PDAC）是导致癌症相关死亡的第七大常见原因。尽管治疗方法多种多样，但仍有将近 90% 以上的胰腺导管腺癌患者在确诊后不久死亡。与在其他癌症中取得的可喜成果相反，免疫检查点抑制剂（ICIs）在 PDAC 中的疗效有限。最近的研究表明，非编码 RNA（ncRNA）广泛参与了 PDAC 细胞与免疫细胞的相互作用，并介导了这种恶性癌症的免疫逃避。PDAC 细胞招募了大量 ncRNA，通过各种机制广泛影响免疫细胞的表型和功能。例如，PDAC 细胞上调 miR-301a 和下调 miR-340 以诱导巨噬细胞 M2 极化，或过度表达 miR-203、miR-146a 和 miR-212-3p 以下调收费样受体 4（TLR4）、CD80、CD86、CD1a、主要组织相容性复合体（MHC）II 和 CD83，从而逃避树突状细胞的识别。通过下调 miR-4299 和 miR-153，PDAC 细胞可以减少 NK 2D 组（NKG2D）和 MHC I 类链相关分子 A 和 B（MICA/B）的表达，从而削弱自然杀伤（NK）细胞的反应。PDAC 细胞还高表达 lncRNA AL137789.1、hsa_circ_0046523、lncRNA LINC00460 和 miR-155-5p，以上调免疫检查点蛋白并逃避 T 细胞的细胞毒性。另一方面，来自抑制性免疫细胞的 ncRNA 可促进 PDAC 细胞的增殖、侵袭和耐药性。ncRNA 可用于克服对 ICIs 的耐药性、监测 PDAC 的免疫微环境并预测对 ICIs 的反应。这篇综述文章全面讨论了有关 ncRNA 在 PDAC 免疫逃避中的作用的最新发现。

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

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