Nemati Mahnaz, Hsu Chou-Yi, Nathiya Deepak, Kumar M Ravi, Oghenemaro Enwa Felix, Kariem Muthena, Kaur Parjinder, Bhanot Deepak, Hjazi Ahmed, Azam Saedi Tayebeh
Amir Oncology Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Thunderbird School of Global Management, Arizona State University, Phoenix, AZ, United States.
Front Immunol. 2025 Apr 9;16:1536428. doi: 10.3389/fimmu.2025.1536428. eCollection 2025.
Gemcitabine (GEM), a nucleoside analog chemotherapy agent, has been widely used in the treatment of various cancers. In recent years, there has been growing interest in understanding the immunomodulatory or immunosuppressive effects of GEM. The immunomodulatory roles of GEM could influence the anti-tumor immune responses via several mechanisms, such as modulation of antigen presentation, cytokine production, and immune cell population. Furthermore, there is evidence that GEM enhances the therapeutic efficacy of immunotherapies, including oncolytic viruses, immune checkpoint inhibitors, CAR T-cells, and therapeutic vaccines. On the other hand, accumulating evidence also proposed that GEM may act as an immunosuppressive agent within the tumor microenvironment, resulting in immune evasion of tumor cells and tumor growth. These paradoxical roles of GEM in modifying immune responses highlight the complexity of GEM interaction with immune cells and responses within the tumor microenvironment. This review aims to provide an overview of the immunomodulatory and immunosuppressive effects of GEM within the tumor microenvironment and how GEM affects the efficacy of cancer immunotherapy.
吉西他滨（GEM）是一种核苷类似物化疗药物，已广泛应用于各种癌症的治疗。近年来，人们对了解吉西他滨的免疫调节或免疫抑制作用的兴趣日益浓厚。吉西他滨的免疫调节作用可通过多种机制影响抗肿瘤免疫反应，如调节抗原呈递、细胞因子产生和免疫细胞群体。此外，有证据表明吉西他滨可增强免疫疗法的治疗效果，包括溶瘤病毒、免疫检查点抑制剂、嵌合抗原受体T细胞和治疗性疫苗。另一方面，越来越多的证据也表明，吉西他滨可能在肿瘤微环境中充当免疫抑制剂，导致肿瘤细胞免疫逃逸和肿瘤生长。吉西他滨在调节免疫反应中的这些矛盾作用凸显了其与肿瘤微环境中免疫细胞和免疫反应相互作用的复杂性。本综述旨在概述吉西他滨在肿瘤微环境中的免疫调节和免疫抑制作用，以及吉西他滨如何影响癌症免疫治疗的疗效。
