Supplementary Figure Legends from The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression

Pushalkar, Smruti; Hundeyin, Mautin; Daley, Donnele; Zambirinis, Constantinos P.; Kurz, Emma; Mishra, Ankita; Mohan, Navyatha; Aykut, Berk; Usyk, Mykhaylo; Torres, Luisana E.; Werba, Gregor; Zhang, Kevin; Guo, Yuanqiang; Li, Qianhao; Akkad, Neha; Lall, Sarah; Wadowski, Benjamin; Gutierrez, Johana; Rossi, Juan Andres Kochen; Herzog, Jeremy; Diskin, Brian; Torres‐Hernandez, Alejandro; Leinwand, Josh; Wang, Wei; Taunk, Pardeep S.; Savadkar, Shivraj; Saxena, Anjana; Li, Xin; Cohen, Deirdre Jill; Sartor, R. Balfour; Saxena, Deepak; Miller, George

doi:10.1158/2159-8290.22532485.v1

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“…[10,11] For example, the mouse pancreatic cancer with abundant tumor-colonizing bacteria such as Actinobacteria, Deferribacteres, and Bifidobacterium exhibited obviously reduced responsive rate to antibodies against programmed cell death protein 1 (anti-PD-1). [12] Among various tumor-colonizing bacteria, Fusobacterium nucleatum is one of the gram-negative anaerobic bacteria and has been reported to accumulate in colorectal tumors and adenomas around colon tissues. [5,10,13,14] Recently, some studies have demonstrated that the enrichment of F. nucleatum in colorectal cancer could drive the formation of immunosuppressive tumor microenvironment (TME), [2] such as increasing the infiltration of immune suppressive cells, [15] decreasing the infiltration of tumor-infiltrating lymphocytes, [2,10] and inhibiting the killing efficiency of NK cells and T cells [16] through direct or indirect interference with metabolic pathways.…”

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confidence: 99%

Antibacterial Fusobacterium nucleatum‐Mimicking Nanomedicine to Selectively Eliminate Tumor‐Colonized Bacteria and Enhance Immunotherapy Against Colorectal Cancer

Chen,

Zhao,

Shen

et al. 2023

Advanced Materials

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Clinical evidence has indicated that tumor‐colonizing bacteria would be closely related to the tumor development and therapeutic responses. Selectively eliminating bacteria within tumors may be an attractive approach to enhance cancer treatment without additional side effects. Herein, we found that owing to the high affinity between the membrane protein Fap‐2 on Fusobacterium nucleatum (F. nucleatum) and D‐galactose‐β (1‐3)‐N‐acetyl‐D‐galactosamine (Gal‐GalNAc) overexpressed on colorectal tumor cells, F. nucleatum would colonize in colorectal tumors, as evidenced by both clinical samples and animal tumor models. Notably, F. nucleatum colonized in colorectal tumors would lead to immunosuppressive tumor microenvironment, greatly reducing their responses to immune checkpoint blockade (ICB) therapy. Inspired by this finding, we designed a F. nucleatum‐mimetic nanomedicine by fusing F. nucleatum cytoplasmic membrane (FM) with Colistin loaded liposomes to achieve selectively killing tumor‐colonizing F. nucleatum without affecting gut microbes. As the results, the therapeutic responses of F. nucleatum‐colonized tumors to ICB therapies could be successfully restored, as demonstrated in F. nucleatum‐infected subcutaneous CT‐26 tumor model, chemical‐induced spontaneous colorectal cancer models and MC‐38 tumor model. In summary, our work presented a F. nucleatum‐Mimicking nanomedicine which could selectively eliminate tumor‐colonized bacteria, promising for enhancing the responses of cancer immunotherapy against F. nucleatum‐colonized colorectal cancer.This article is protected by copyright. All rights reserved

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