The relationship between gastrointestinal (GI) bacteria and the response to anti-CTLA-4 and anti-PD-1 immunotherapy in the treatment of cancer can potentially be enhanced to allow patients to maximally respond to these treatments. Insight into the complex interaction between gut microbiota and the human adaptive immune system will help guide future immunotherapeutic cancer treatments to allow a more robust clinical response and fewer adverse effects in patients requiring these drugs. This review highlights these interactions as well as the potential for the creation of “oncomicrobiotics” that would selectively tailor one’s GI bacteria to maximally respond to anti-CTLA-4 and anti-PD-1 treatments will fewer adverse effects. CTLA-4 is an antigen on the surface of T cells which, upon stimulation, leads to inhibition of activated T cells to terminate the immune response. However, many types of tumor cells can upregulate CTLA-4 in the tumor microenvironment, allowing these cells to evade targeting and destruction by the body’s immune system by prematurely inhibiting T cells. Increased representation of Bacteroides fragilis, Burkholderia cepacia and the Faecalibacterium genus in the GI tract of patients receiving CTLA-4-based immunotherapy led to a stronger therapeutic effect while minimizing adverse side effects such as colitis. In addition, by introducing bacteria involved in vitamin B and polyamine transport to the GI tracts of patients treated with anti-CTLA-4 drugs led to increased resistance to colitis while maintaining therapeutic efficacy. PD-1 is another molecule upregulated in many tumor microenvironments which acts in a similar manner to CTLA-4 to tone down the anti-neoplastic actions of T cells. Antibodies to PD-1 have shown promise to help allow the body’s natural immune response to appropriately target and destroy tumor cells. The presence of Bifidobacterium breve and longum, Akkermansia muciniphila and Faecalibacterium prausnitzii in the GI tracts of cancer patients has the potential to create a more robust immune response to anti-PD-1 drugs and prolonged survival. The development of “oncomicrobiotics” has the potential to help tailor one’s gut microbiota to allow patients to maximally respond to immunotherapy without sacrificing increases in toxicity. These oncomicrobiotics may possibly include antibiotics, probiotics, postbiotics and/or prebiotics. However, many challenges lie ahead in the creation of oncomicrobiotics. The creation of oncomicrobiotics may allow many patients receiving anti-CTLA-4 and PD-1 immunotherapy to experience prolonged survival and a better quality of life.

中文翻译：

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基于 CTLA-4 和 PD-1 的免疫疗法治疗癌症的机制和微生物影响：叙述性综述。

胃肠道 (GI) 细菌与抗 CTLA-4 和抗 PD-1 免疫疗法在癌症治疗中的反应之间的关系可能会得到加强，以使患者对这些治疗产生最大的反应。深入了解肠道微生物群与人类适应性免疫系统之间的复杂相互作用将有助于指导未来的免疫治疗癌症治疗，从而使需要这些药物的患者获得更强大的临床反应和更少的不良反应。这篇综述强调了这些相互作用以及创造“肿瘤微生物”的潜力，这种微生物可以选择性地调整一个人的胃肠道细菌，以最大限度地响应抗 CTLA-4 和抗 PD-1 治疗，从而减少不良反应。CTLA-4 是 T 细胞表面的抗原，在受到刺激时，导致抑制活化的T细胞以终止免疫反应。然而，许多类型的肿瘤细胞可以上调肿瘤微环境中的CTLA-4，使这些细胞通过过早地抑制T细胞来逃避机体免疫系统的靶向和破坏。在接受基于 CTLA-4 的免疫治疗的患者的胃肠道中，脆弱拟杆菌、洋葱伯克霍尔德菌和粪杆菌属的代表性增加导致更强的治疗效果，同时最大限度地减少结肠炎等不良副作用。此外，通过将参与维生素 B 和多胺转运的细菌引入接受抗 CTLA-4 药物治疗的患者的胃肠道，可以增加对结肠炎的抵抗力，同时保持治疗效果。PD-1 是另一种在许多肿瘤微环境中上调的分子，其作用方式与 CTLA-4 相似，可减弱 T 细胞的抗肿瘤作用。PD-1 抗体已显示出有助于使身体的自然免疫反应适当地靶向和破坏肿瘤细胞的前景。癌症患者的胃肠道中存在短双歧杆菌和长双歧杆菌、嗜粘液阿克曼氏菌和普氏粪杆菌有可能对抗 PD-1 药物产生更强大的免疫反应并延长生存期。“肿瘤微生物”的发展有可能帮助调整一个人的肠道微生物群，让患者在不牺牲毒性增加的情况下最大限度地响应免疫疗法。这些致癌微生物可能包括抗生素、益生菌、后生元和/或益生元。然而，在创造肿瘤微生物方面面临着许多挑战。肿瘤微生物的产生可能使许多接受抗 CTLA-4 和 PD-1 免疫治疗的患者能够延长生存期和提高生活质量。