Project Details
Projekt
The role of plasma cell activation and metabolism in colorectal carcinogenesis and metastasis
Subject Area
Gastroenterology
Term
from 2019 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 280163318
In the last decade the focus for cancer treatment has moved away from drugs that target the tumor broadly or just the tumor cells themselves (like chemotherapy and radiation) towards immunotherapies that affect distinct cells and cell interaction in the tumor microenvironment. Although the recent advancement of immunotherapy was encouraging, and many patients have achieved significant benefits, the vast majority of patients still do not respond to immunotherapy, partly due to the complexity and diversity of the tumor microenvironment. In colorectal cancer (CRC) research largely concentrates on the role of T cells and antigen presenting cells in the tumor microenvironment. However, CRCs are infiltrated by diverse B cell subsets, but their roles in colorectal carcinogenesis are largely unknown. In the last funding period, we could show that human colorectal carcinoma – particularly at the invasive margin – are enriched in infiltrating B cells consisting of naïve, memory B cells and plasma cells. Thus distinct B cell subsets present in the tumor microenvironment influence the prognosis of CRC patients either positively or negatively. In mechanistic analysis we have shown that B cells set the stage for anti-tumoral immune responses in the tumor microenvironment of colorectal cancer via induction of innate lymphoid cells (ILC) as well as cytotoxic T and NK cell responses, while at the same time dampening cellular immunosuppressive effects. Specifically, our results lead to the hypothesis that these anti-tumoral functions are induced by tumor-infiltrating bacteria engaging pattern recognition receptor (PRR) signaling in plasma cells with consecutive inflammasome activation. Therefore, we will analyze PRR signaling in plasma cells in the tumor microenvironment of colorectal cancer and its impact on anti-tumoral immune responses. These anti-tumoral effects are potentially built on metabolic reprogramming of tumor-infiltrating plasma cells, as we could demonstrate altered metabolic profiles of human tumor-infiltrating B cells.
DFG Programme
Research Units
Subproject of
FOR 2438:
Cell Plasticity in Colorectal Carcinogenesis
