CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Role of Short-Chain Fatty Acids, Particularly Butyrate, in Oncological Immunotherapy with Checkpoint Inhibitors: The Effectiveness of Complementary Treatment with Clostridium butyricum 588.
The Role of Short-Chain Fatty Acids, Particularly Butyrate, in Oncological Immunotherapy with Checkpoint Inhibitors: The Effectiveness of Complementary Treatment with Clostridium butyricum 588.
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免疫检查点(CTLA-4、PD-1 和 PD-L1)的发现及其对肿瘤疾病预后的影响,为革命性肿瘤治疗的发展铺平了道路。这些治疗并非用“对抗”癌细胞的药物来抗击肿瘤,而是支持和增强免疫系统直接对肿瘤生长作出反应的能力,即通过淋巴细胞攻击癌细胞。目前已广泛证实,充分的免疫反应——本质上以肿瘤团块中存在的 TIL(肿瘤浸润淋巴细胞)数量为代表——对治疗反应和疾病预后具有决定性影响。
因此,免疫治疗的基础在于能够增加肿瘤部位淋巴细胞的存在,从而限制并消除某些肿瘤逃逸机制,特别是那些由检查点活性(在正常生理条件下)所表达的、抑制针对转化细胞反应的机制,否则免疫治疗无法实施。免疫治疗已处于实验阶段数十年,其优异的结果使其成为许多肿瘤病理治疗的基石,尤其是与化疗和放疗联合使用时。尽管取得了这些成功,仍有相当数量的患者(约 50%)对治疗无反应或早期即产生耐药。微生物群、其组成以及我们调节它的能力,可以对肿瘤治疗产生积极影响,减少副作用并提高敏感性和有效性。发表在高影响力期刊上的大量研究证实,某种微生物平衡,特别是能够产生短链脂肪酸(SCFAs)、尤其是丁酸的细菌的存在,不仅对于减少放化疗治疗的副作用至关重要,而且对于更好的免疫治疗反应以及因此更好的预后也至关重要。这开辟了一种可能性,即对微生物群进行有利调控可能成为标准肿瘤治疗的重要补充治疗。这篇简要综述旨在强调使用精准益生菌(如产丁酸的丁酸梭菌)来改善免疫检查点治疗反应、从而改善肿瘤疾病预后的关键方面。
The discovery of immune checkpoints (CTLA-4, PD-1, and PD-L1) and their impact on the prognosis of oncological diseases have paved the way for the development of revolutionary oncological treatments. These treatments do not combat tumors with drugs "against" cancer cells but rather support and enhance the ability of the immune system to respond directly to tumor growth by attacking the cancer cells with lymphocytes.
It has now been widely demonstrated that the presence of an adequate immune response, essentially represented by the number of TILs (tumor-infiltrating lymphocytes) present in the tumor mass decisively influences the response to treatments and the prognosis of the disease.
Therefore, immunotherapy is based on and cannot be carried out without the ability to increase the presence of lymphocytic cells at the tumor site, thereby limiting and nullifying certain tumor evasion mechanisms, particularly those expressed by the activity (under positive physiological conditions) of checkpoints that restrain the response against transformed cells. Immunotherapy has been in the experimental phase for decades, and its excellent results have made it a cornerstone of treatments for many oncological pathologies, especially when combined with chemotherapy and radiotherapy. Despite these successes, a significant number of patients (approximately 50%) do not respond to treatment or develop resistance early on. The microbiota, its composition, and our ability to modulate it can have a positive impact on oncological treatments, reducing side effects and increasing sensitivity and effectiveness.
Numerous studies published in high-ranking journals confirm that a certain microbial balance, particularly the presence of bacteria capable of producing short-chain fatty acids (SCFAs), especially butyrate, is essential not only for reducing the side effects of chemoradiotherapy treatments but also for a better response to immune treatments and, therefore, a better prognosis.
This opens up the possibility that favorable modulation of the microbiota could become an essential complementary treatment to standard oncological therapies. This brief review aims to highlight the key aspects of using precision probiotics, such as Clostridium butyricum , that produce butyrate to improve the response to immune checkpoint treatments and, thus, the prognosis of oncological diseases.
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