Melody Zeng, Associate Professor of Immunology in Pediatrics at Weill Cornell Medicine, shared a post on LinkedIn:
“Excited to share the newest work from my lab – out in Cancer Cell by Cell Press: “Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth”! This work was led led by my talented postdoc Hilal bashir, with support from many other members of my lab.
How does chronic stress affect our gut microbiome – and would these changes of our gut microbiome impact how our immune system responds to tumors?
By studying mouse models of colorectal cancer and melanoma, as well as human colon or brain tumors, we discovered that chronic stress triggers a mild gut permeability that allows bacteria with lytic phages (including Enterococcus gallinarum in mice and Klebsiella pneumoniaea in humans) that traffic to tumors. Within tumors, these phages induce cancer-associated fibroblasts (CAFs) via TLR9 to produce glucocorticoids, resulting in a local source of glucocorticoids that directly suppresses anti-tumor germinal center B cell responses via the glucocorticoid receptor NR3C1 – forming a pro-tumor circuit that accelerates cancer progression.
This work reveals a novel transkingdom microbiome-phage-fibroblasts-B cell axis connecting chronic psychological stress to worse cancer outcomes, opening new avenues for therapeutic intervention.
This is the first cancer research paper out of my lab! Grateful to our outstanding collaborators, including Gregory F. Sonnenberg, Patrick C. Wilson, David Lyden, Irina Matei at Weill Cornell Medicine, Naohiro Inohara at University of Michigan, Mikala Egeblad at The Johns Hopkins University, Han Sang Kim at Yonsei University, and Jayanta Chaudhuri at Memorial Sloan Kettering Cancer Center.
Really apperciate the contructive feedback and helpful suggestions from all reviewers and outstanding guidance by the editor.”
Title: Chronic stress unleashes an intratumor phage-fibroblast-B cell circuit to promote tumor growth
Authors: Hilal Bashir, Katherine Z. Sanidad, Purnima Ravisankar, Kelly M. Banks, Avipsa Bose, Shui Yu, Joshua J. C. McGrath, Hannah C. Carrow, Taeyul K. Kim, Chloe A. Troxell, Julia A. Brown, Lucy R. Hart, Jeremy Goc, Mikala Egeblad, Jayanta Chaudhuri, Han Sang Kim, Patrick C. Wilson, David C. Lyden, Irina R. Matei, Naohiro Inohara, Melody Y. Zeng
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