慢性应激释放肿瘤内吞噬纤维母细胞-B细胞回路，促进肿瘤生长
Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.
摘要(中文译文)
慢性压力会破坏癌症患者的肠道微生物群；然而，压力诱导的微生物群扰动如何影响抗肿瘤免疫尚不清楚。在这里，我们表明肠道微生物群是慢性应激诱导的糖皮质激素产生所必需的，这会损害抗原特异性生发中心B细胞反应。在癌症或黑色素瘤的小鼠模型中，慢性应激促进肠道致病菌，即鸡肠球菌（Eg）转移到肿瘤中。在肿瘤中，Eg噬菌体DNA通过TLR9诱导癌症相关成纤维细胞（CAFs）产生糖皮质激素，TLR9通过糖皮质激素受体抑制抗肿瘤B细胞反应。靶向肿瘤内TLR9或Eg可显著降低肿瘤内糖皮质激素水平，并逆转慢性应激的促肿瘤作用。将这些发现扩展到人类癌症，我们从人类结肠直肠肿瘤中鉴定了肺炎克雷伯菌分离株中促进肿瘤生长的裂解性噬菌体，并检测了人类脑肿瘤中的噬菌体DNA。总之，我们的研究揭示了一种慢性应激诱导的肿瘤内噬菌体-CAF-B细胞回路，该回路会削弱抗肿瘤免疫。
Abstract
Chronic stress disrupts the gut microbiota in patients with cancer; however, how stress-induced microbiota perturbations impact anti-tumor immunity remains unclear. Here, we show that the gut microbiota is required for chronic stress-induced glucocorticoid production, which impairs antigen-specific germinal center B cell responses. In mouse models of colorectal cancer or melanoma, chronic stress promotes translocation of a gut pathobiont, Enterococcus gallinarum (Eg), to tumors. Within tumors, Eg phage DNA induces glucocorticoid production by cancer-associated fibroblasts (CAFs) via TLR9, which suppresses anti-tumor B cell responses through the glucocorticoid receptor. Targeting intratumoral TLR9 or Eg significantly lowers intratumor glucocorticoid levels and reverses the tumor-promoting effects of chronic stress. Extending these findings to human cancer, we identify lytic phages in a Klebsiella pneumoniae isolate from human colorectal tumors that promote tumor growth and detect phage DNA in human brain tumors. Together, our study reveals a chronic stress-induced intratumor phage-CAF-B cell circuit that weakens anti-tumor immunity.
如何引用
AMA
Hilal Bashir, Katherine Z Sanidad, Purnima Ravisankar, Kelly M Banks, Avipsa Bose, Shui Yu, et al. Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.. Cancer cell. 2026; doi:10.1016/j.ccell.2026.06.004.
APA
Hilal Bashir, Katherine Z Sanidad, Purnima Ravisankar, Kelly M Banks, Avipsa Bose, Shui Yu, et al (2026). Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.. Cancer cell. https://doi.org/10.1016/j.ccell.2026.06.004
GB/T 7714
Hilal Bashir, Katherine Z Sanidad, Purnima Ravisankar, Kelly M Banks, Avipsa Bose, Shui Yu, et al. Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth.[J]. Cancer cell, 2026 doi:10.1016/j.ccell.2026.06.004.
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