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Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Evaluating the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1).
The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints.
The findings are the first to demonstrate a link between a genetically defined subtype of cancer and its corresponding expression of immune checkpoints in the tumor microenvironment, and suggest that blockade of specific checkpoints may be selectively efficacious in the MSI subset of colorectal cancer.
A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses
Results show a Stat3- and TH17-dependent pathway for inflammation-induced cancer by a common human commensal bacterium, providing new mechanistic insight into human colon carcinogenesis.
Cutting Edge: An In Vivo Requirement for STAT3 Signaling in TH17 Development and TH17-Dependent Autoimmunity1
In vivo evidence is provided that the fundamental role of STAT3 signaling in autoimmunity relates to its absolute requirement for generating TH17 T cell responses, and STAT3 is a candidate target for TH17-dependent autoimmune disease immunotherapy that could selectively inhibit pathogenic immune pathways.
Microbiota organization is a distinct feature of proximal colorectal cancers
- Christine M Dejea, E. Wick, C. Sears
- Biology, MedicineProceedings of the National Academy of Sciences
- 8 December 2014
It is demonstrated for the first time that bacterial biofilms are associated with colorectal cancers, one of the leading malignancies in the United States and abroad, and that the mucosal microbiota organization is a critical factor associated with a subset of CRC.
Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity
In vivo, splenic IKDCs preferentially show NK function and, upon systemic infection, migrate to lymph nodes, where they primarily show antigen-presenting cell activity, which formally distinguish them from classical NK cells.
Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria
Genes for colibactin and Bacteroides fragilis toxin, encoding secreted oncotoxins, were highly enriched in FAP patients’ colonic mucosa compared to healthy individuals, suggesting an unexpected link between early neoplasia of the colon and tumorigenic bacteria.
Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia.
Developing a pro-regenerative biomaterial scaffold microenvironment requires T helper 2 cells
It is investigated how biomaterial scaffolds shape the immune microenvironment in traumatic muscle wounds to improve tissue regeneration and Manipulating the adaptive immune system using biomaterials engineering may support the development of therapies that promote both systemic and local pro-regenerative immune responses, ultimately stimulating tissue repair.
Induction of Persistent Colitis by a Human Commensal, Enterotoxigenic Bacteroides fragilis, in Wild-Type C57BL/6 Mice
The hypothesis that chronic colonization with the human commensal ETBF can induce persistent, subclinical colitis in humans is supported.