Dayhimi Amir, Jazi Kimia, Bigdeli Asiye, Farhoudi Fatemeh, Erfanimanesh Mohamadreza, Esmaeili Mina, Gorjipour Farhad, Ajami Marjan, Pazoki-Toroudi Hamidreza
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Technol Cancer Res Treat. 2025 Jan-Dec;24:15330338251365700. doi: 10.1177/15330338251365700. Epub 2025 Aug 28.
IntroductionImmunotherapy approaches have improved by Immune check point inhibitors such as PD-1, CTLA-4, and PD-L1 inhibitors. However, the response to immunotherapy varies widely among patients due to various factors. Co-administration of probiotics with ICIs has become a promising strategy to improve therapeutic outcomes. This review evaluates the impact of environmental factors and life style on cancer pathophysiology, outcome of disease, and response to the treatment. It evaluates the role of probiotics in modulating immune responses and the synergistic interaction of probiotics with immunotherapy.MethodsWe conducted a comprehensive systematic review of clinical and preclinical studies to assess the effects of probiotics on immunotherapy outcomes. Studies were selected based on their focus on probiotics' role in immune response modulation and interaction with ICIs. Data from trials involving patients with varying responses to immunotherapy, including those with prior resistance, were analyzed to explore the probiotic-enhanced immunotherapy.ResultsGut microbiome has wide effects on immune responses through different pathways like production of short chain fatty acids (SCFAs), polysaccharide A, and indole-3-carbaldehyde. Also, probiotics found to enhance Anit-inflammatory responses and increase CD8+ T-cell activity, suggesting a synergistic effect with ICIs. Gut microbiota composition plays a key role in determining the effectiveness of immunotherapy, especially in treatment-resistant patients. For optimized treatment outcomes, personalized probiotics tailored to individual's microbiota showed potential. Important challenges are treatment resistance and compromised mucosal integrity because of microbiome alterations. Effective drug delivery also remains as important barriers to common adoption.ConclusionFor immunotherapy outcomes improvement, immune responses modulation and gut microbiome diversity enhancement show probiotics important promise. Despite their potential, limitations must be addressed including treatment resistance and also delivery challenges. In order to maximize therapeutic benefits, personalized probiotic strategies have to be developed, and also the mechanisms by which probiotics improve ICI efficacy require elucidation through further research.
引言
免疫疗法因免疫检查点抑制剂如PD-1、CTLA-4和PD-L1抑制剂而得到改善。然而，由于各种因素，患者对免疫疗法的反应差异很大。益生菌与免疫检查点抑制剂联合使用已成为改善治疗效果的一种有前景的策略。本综述评估了环境因素和生活方式对癌症病理生理学、疾病结局和治疗反应的影响。它评估了益生菌在调节免疫反应中的作用以及益生菌与免疫疗法的协同相互作用。
方法
我们对临床和临床前研究进行了全面的系统评价，以评估益生菌对免疫治疗结果的影响。研究的选择基于其对益生菌在免疫反应调节中的作用以及与免疫检查点抑制剂相互作用的关注。分析了涉及对免疫疗法有不同反应的患者（包括先前有耐药性的患者）的试验数据，以探索益生菌增强的免疫疗法。
结果
肠道微生物群通过不同途径对免疫反应有广泛影响，如短链脂肪酸（SCFAs）、多糖A和吲哚-3-甲醛的产生。此外，发现益生菌可增强抗炎反应并增加CD8+T细胞活性，表明与免疫检查点抑制剂有协同作用。肠道微生物群组成在决定免疫疗法的有效性方面起着关键作用，尤其是在治疗耐药患者中。为了获得优化的治疗结果，针对个体微生物群定制的个性化益生菌显示出潜力。重要的挑战是由于微生物群改变导致的治疗耐药性和粘膜完整性受损。有效的药物递送也仍然是广泛应用的重要障碍。
结论
为了改善免疫治疗结果，调节免疫反应和增强肠道微生物群多样性显示出益生菌具有重要前景。尽管它们有潜力，但必须解决包括治疗耐药性和递送挑战在内的局限性。为了最大限度地提高治疗益处，必须制定个性化的益生菌策略，并且还需要通过进一步研究阐明益生菌改善免疫检查点抑制剂疗效的机制。
