Microbiota Manipulation as an Emerging Concept in Cancer Therapy.

Background: The human body is colonized by billions of bacteria that provide nutrients to the host, train our immune system, and importantly affect our heath. It has long been suggested that microbes might play a role in tumor pathogenesis; however, compelling evidence was only provided in the past decades when novel detection methods that do not depend on culturing techniques had been developed.

Summary: The microbiome impacts tumor development and anti-tumor therapies on various levels.

SKAP2-A Molecule at the Crossroads for Integrin Signalling and Immune Cell Migration and Function.

Src-kinase associated protein 2 (SKAP2) is an intracellular scaffolding protein that is broadly expressed in immune cells and is involved in various downstream signalling pathways, including, but not limited to, integrin signalling. SKAP2 has a wide range of binding partners and fine-tunes the rearrangement of the cytoskeleton, thereby regulating cell migration and immune cell function. Mutations in SKAP2 have been associated with several inflammatory disorders such as Type 1 Diabetes and Crohn's disease.

Co-cultivation is a powerful approach to produce a robust functionally designed synthetic consortium as a live biotherapeutic product (LBP).

The success of fecal microbiota transplants (FMT) has provided the necessary proof-of-concept for microbiome therapeutics. Yet, feces-based therapies have many associated risks and uncertainties, and hence defined microbial consortia that modify the microbiome in a targeted manner have emerged as a promising safer alternative to FMT. The development of such live biotherapeutic products has important challenges, including the selection of appropriate strains and the controlled production of the consortia at scale.

Inhibition of integrin αvβ6 sparks T-cell antitumor response and enhances immune checkpoint blockade therapy in colorectal cancer.

Background: Integrin αvβ6 is a heterodimeric cell surface protein whose cellular expression is determined by the availability of the integrin β6 subunit (ITGB6). It is expressed at very low levels in most organs during tissue homeostasis but shows highly upregulated expression during the process of tumorigenesis in many cancers of epithelial origin. Notably, enhanced expression of integrin αvβ6 is associated with aggressive disease and poor prognosis in numerous carcinoma entities.

Autoimmune susceptibility gene is required for clearance of adherent-invasive by integrating bacterial uptake and lysosomal defence.

Objectives: Alterations in the intestinal microbiota are linked with a wide range of autoimmune and inflammatory conditions, including inflammatory bowel diseases (IBD), where pathobionts penetrate the intestinal barrier and promote inflammatory reactions. In patients with IBD, the ability of intestinal macrophages to efficiently clear invading pathogens is compromised resulting in increased bacterial translocation and excessive immune reactions. Here, we investigated how an IBD-associated loss-of-function variant in the protein tyrosine phosphatase non-receptor type 2 () gene, or loss of PTPN2 expression affected the ability of macrophages to respond to invading bacteria.