Translational Cancer Genomics Group, Danish Cancer Institute, Copenhagen, Denmark.
Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.
Oncoimmunology. 2024 Mar 4;13(1):2324493. doi: 10.1080/2162402X.2024.2324493. eCollection 2024.
Immune checkpoint inhibitor therapy has dramatically improved survival in a significant subset of patients with several solid tumor types. Increasing the number of patients benefitting from this form of therapy is an important translational research goal. Correlations between the composition of the gut microbiome and response to immune checkpoint inhibitor therapy raised the possibility that direct modulation of the gut microbiome may significantly improve the clinical benefit of this treatment. Several lines of observations suggest that tumor-associated carbohydrates, including those recognized as blood group-related glycolipid antigens, such as the Forssman antigen, may be some of the key factors behind this clinical correlation. Such antigens are expressed in human cancer, humans often produce antibodies against those, and they can induce antibody directed cellular cytotoxicity. Importantly, these antibodies are often induced by antigens present in microbes of the gut. If identified, these antibodies could be boosted by appropriate vaccination techniques and thus enhance anti-tumor immunity with minimal side effects.
免疫检查点抑制剂治疗在几种实体肿瘤类型的显著亚组患者中显著提高了生存率。增加受益于这种治疗形式的患者数量是一个重要的转化研究目标。肠道微生物组的组成与免疫检查点抑制剂治疗反应之间的相关性提出了这样一种可能性，即直接调节肠道微生物组可能显著提高这种治疗的临床获益。有几条观察结果表明，肿瘤相关碳水化合物，包括那些被认为是血型相关糖脂抗原的碳水化合物，如 Forssman 抗原，可能是这种临床相关性背后的一些关键因素。这些抗原在人类癌症中表达，人类通常会产生针对这些抗原的抗体，并且它们可以诱导抗体定向细胞毒性。重要的是，这些抗体通常是由肠道微生物中的抗原诱导产生的。如果这些抗体被识别出来，可以通过适当的疫苗接种技术来增强，从而在最小的副作用下增强抗肿瘤免疫力。
