Zhao Yuemei, Liu Weidong, Hu Yuehong
Department of Surgery and Critical Care Medicine, Shaoxing People's Hospital, Zhejiang Province, ShaoxingShaoxing City, 312000, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 3. doi: 10.1007/s00210-025-04315-4.
Cancer immunotherapy aims to use the immune system of the body for improved therapeutic effects on tumors. Currently, one of the more encouraging interventions under evaluation involves the use of immune checkpoint blockade, which offers longer benefit periods and greater patient tolerance than previous interventions for solid malignancies. Nevertheless, a majority of patients never respond or gradually acquire resistance; hence, a suboptimal effect of the therapy ensues. Resistance to such treatments may arise from tumor-specific factors, host factors, and environmental influences. There is growing evidence that the gut microbiome is an important modulator not only of the efficacy of these treatments but also of toxicities. Current studies are focused on the identification of key microbial profiles from both preclinical and clinical samples associated with immunotherapeutic response and antitumor activities. Elucidation of this complex interaction may provide ways to modulate gut microbial communities to improve patient outcomes. The current review addresses the components responsible for resistance against immune checkpoint inhibitors and highlights the crucial linkage between gut microbiome-immune interactions. We further summarize some recent clinical findings and explore prospective avenues for research in this evolving area of cancer treatment.
癌症免疫疗法旨在利用人体免疫系统来提高对肿瘤的治疗效果。目前，正在评估的一项更令人鼓舞的干预措施是使用免疫检查点阻断疗法，与以往治疗实体恶性肿瘤的干预措施相比，该疗法的受益期更长，患者耐受性更高。然而，大多数患者从未产生反应或逐渐产生耐药性；因此，治疗效果欠佳。对此类治疗的耐药性可能源于肿瘤特异性因素、宿主因素和环境影响。越来越多的证据表明，肠道微生物群不仅是这些治疗疗效的重要调节因子，也是毒性的重要调节因子。目前的研究集中在从临床前和临床样本中识别与免疫治疗反应和抗肿瘤活性相关的关键微生物特征。阐明这种复杂的相互作用可能会提供调节肠道微生物群落以改善患者预后的方法。本综述阐述了对免疫检查点抑制剂产生耐药性的相关因素，并强调了肠道微生物群与免疫相互作用之间的关键联系。我们进一步总结了一些近期的临床发现，并探索了这一不断发展的癌症治疗领域的未来研究方向。
