Project Details
Projekt
Clinical significance of the local and systemic immunologic microenvironment in patients with colorectal cancer liver metastases
Applicants
Privatdozent Dr. Niels Halama; Inka Zörnig, Ph.D.
Subject Area
General and Visceral Surgery
Term
from 2012 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 101804013
It has been recently shown that the clinical outcome of patients with colorectal cancer (CRC) is greatly influenced by immune responses at the tumor site. T cell infiltrates in primary CRC, especially memory T cells, correlate with a more favorable prognosis whereas patients with CRC that have low densities of infiltrating T cells have a poor prognosis, independent of the tumor stage. This applies to the metastatic disease situation. The link between the local immunological microenvironment and the systemic environment has not been systematically analyzed. In contrast to cellular anti-tumor immune responses it is especially unknown to date if tumor associated antigen (TAA)-specific antibody responses mediate an anti-tumor effect in vivo or if they just represent an epiphenomenon of ongoing effective - or ineffective T cell responses. To better understand the immunological effector mechanisms of anti-tumor responses we will analyze the cytokine and chemokine profile in CRC liver metastases as well as immune cell densities and distributions and correlate those findings with cytokine profiles and TAA-specific antibody responses in patients´ sera. Whole-slide imaging of histological sections coupled with automatic image processing, microdissection and multiplex protein quantification technologies have been established, as well as multiplex serology. Linking these detailed immunological profiles with clinical data allows to identify key biomarkers and factors in the intricate interplay between these compartments. Identification of prognostic and predictive serum markers for treatment decisions will improve patient stratification and subsequent clinical routine.
DFG Programme
Clinical Research Units
Participating Person
Professor Dr. Dirk Jäger
