Determing the cellular immunophenotype-genotype interactions in pancreatic cancer towards targeted personalized immunotherapies

The objective treatment response of patients with advanced staged tumors
treated with anti-CTLA4, -PD-1, or *PD-L1 antibodies is very encouraging. Most
of the current immunotherapies work at least in part by activating the immune
system to target the tumor cells. But without knowing the immune competence of
a particular patient, such strategies may fail, or work only in a fraction of
patients. To date immunotherapies have not shown much promise for patients with
Pancreatic Ductal Adenocarcinoma(PDAC). This observation suggests that a deeper
understanding of the phenotype-genotype interactions and genetic heterogeneity
is necessary before one can envision personalized immunotherapeutics.

The global aim of this project is to determine the immunophenotype-genotype
interactions of PC. The novel insights in the molecular genomic and
immunological profile of the tumor tissue and metastases are expected to help
determine the immune activation within PC patients. This approach helps the
development of effective immune therapy in PC and in turn could predict whether
patients would benefit from targeted personalized immunotherapies.

This is a preclinical study with translational focus. The immune Tumor
Micro-Environment (TME) of resected pancreatic tumors and associated lymph
nodes will be analyzed by mass cytometry and correlated with the analysis of
peripheral- and portal vein blood samples of the same patients. Furthermore,
Next Generation Sequencing(NGS)-based analysis of tumor genomes and
transcriptomes will be performed in order to correlate gene expression and
mutation profiles with the immunophenotypes found in the TME.

The burden or risks for patients are minimal as studies will be performed on
material derived from regular surgical procedures as well as from blood samples
collected through venapuncture. We asked the patient enrolled to give 50mL (5
tubes) of blood before the operation and 50 ml(5 tubes) after the operation
whilst still in the hospital. Afterwards the collection of blood samples will
be combined with the outpatient clinic appointments, so as to not cause any
inconvenience for the patients.