Targeting the metabolism and immune system in pancreatic ductal adenocarcinoma: Insights and future directions

IF 9.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine & Growth Factor Reviews Pub Date : 2023-06-01 DOI:10.1016/j.cytogfr.2023.06.006

Dhana Sekhar Reddy Bandi , Sujith Sarvesh , Batoul Farran , Ganji Purnachandra Nagaraju , Bassel F. El-Rayes

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引用次数: 1

Abstract

Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), presents a challenging landscape due to its complex nature and the highly immunosuppressive tumor microenvironment (TME). This immunosuppression severely limits the effectiveness of immune-based therapies. Studies have revealed the critical role of immunometabolism in shaping the TME and influencing PDAC progression. Genetic alterations, lysosomal dysfunction, gut microbiome dysbiosis, and altered metabolic pathways have been shown to modulate immunometabolism in PDAC. These metabolic alterations can significantly impact immune cell functions, including T-cells, myeloid-derived suppressor cells (MDSCs), and macrophages, evading anti-tumor immunity. Advances in immunotherapy offer promising avenues for overcoming immunosuppressive TME and enhancing patient outcomes. This review highlights the challenges and opportunities for future research in this evolving field. By exploring the connections between immunometabolism, genetic alterations, and the microbiome in PDAC, it is possible to tailor novel approaches capable of improving immunotherapy outcomes and addressing the limitations posed by immunosuppressive TME. Ultimately, these insights may pave the way for improved treatment options and better outcomes for PDAC patients.

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针对胰腺导管腺癌的代谢和免疫系统:见解和未来方向

胰腺癌症，特别是胰腺导管腺癌（PDAC），由于其复杂的性质和高度免疫抑制的肿瘤微环境（TME），呈现出具有挑战性的前景。这种免疫抑制严重限制了基于免疫的治疗的有效性。研究揭示了免疫代谢在TME形成和影响PDAC进展中的关键作用。遗传改变、溶酶体功能障碍、肠道微生物组失调和代谢途径的改变已被证明可以调节PDAC的免疫代谢。这些代谢变化可以显著影响免疫细胞功能，包括T细胞、骨髓源性抑制细胞（MDSCs）和巨噬细胞，从而逃避抗肿瘤免疫。免疫疗法的进展为克服免疫抑制性TME和提高患者预后提供了有希望的途径。这篇综述强调了这一不断发展的领域未来研究的挑战和机遇。通过探索PDAC中免疫代谢、基因改变和微生物组之间的联系，有可能定制能够改善免疫治疗结果并解决免疫抑制TME带来的局限性的新方法。最终，这些见解可能为改善PDAC患者的治疗选择和更好的结果铺平道路。

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来源期刊

Cytokine & Growth Factor Reviews 生物-生化与分子生物学

CiteScore

21.10

自引率

1.50%

发文量

审稿时长

22 days

期刊介绍： Cytokine & Growth Factor Reviews is a leading publication that focuses on the dynamic fields of growth factor and cytokine research. Our journal offers a platform for authors to disseminate thought-provoking articles such as critical reviews, state-of-the-art reviews, letters to the editor, and meeting reviews. We aim to cover important breakthroughs in these rapidly evolving areas, providing valuable insights into the multidisciplinary significance of cytokines and growth factors. Our journal spans various domains including signal transduction, cell growth and differentiation, embryonic development, immunology, tumorigenesis, and clinical medicine. By publishing cutting-edge research and analysis, we aim to influence the way researchers and experts perceive and understand growth factors and cytokines. We encourage novel expressions of ideas and innovative approaches to organizing content, fostering a stimulating environment for knowledge exchange and scientific advancement.