Bandi Dhana Sekhar Reddy, Sarvesh Sujith, Farran Batoul, Nagaraju Ganji Purnachandra, El-Rayes Bassel F
Department of Hematology and Oncology, Heersink School of Medicine, University of Alabama, Birmingham, AL 35233, USA.
Department of Oncology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cytokine Growth Factor Rev. 2023 Jun-Aug;71-72:26-39. doi: 10.1016/j.cytogfr.2023.06.006. Epub 2023 Jun 30.
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.
胰腺癌，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局面。这种免疫抑制严重限制了基于免疫的疗法的有效性。研究揭示了免疫代谢在塑造TME和影响PDAC进展中的关键作用。基因改变、溶酶体功能障碍、肠道微生物群失调和代谢途径改变已被证明可调节PDAC中的免疫代谢。这些代谢改变可显著影响免疫细胞功能，包括T细胞、髓源性抑制细胞（MDSC）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和改善患者预后提供了有希望的途径。本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、基因改变和微生物群之间的联系，有可能定制新的方法，提高免疫治疗效果，并解决免疫抑制性TME带来的局限性。最终，这些见解可能为改善PDAC患者的治疗选择和预后铺平道路。
