Objective: To determine which co-stimulatory and -inhibitory molecules are expressed on tumor-infiltrating lymphocytes (TIL) derived from patients with CCA, and to study the effects of targeting these molecules on their function in ex vivo assays.
ID
Source
Brief title
Condition
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are:
1) Frequencies and absolute cell counts of different lymphocyte populations
that together compose the tumor-infiltrating lymphocyte pool.
2) Expression of co-stimulatory/co-inhibitory molecules on TIL vs lymphocytes
isolated from tumor-free liver tissue vs circulating lymphocytes
3) Effect of blocking co-inhibitory molecules or stimulating co-stimulatory
molecules expressed by TIL on their function (proliferation and cytokine
production) in ex vivo co-culture experiments
Secondary outcome
Depending on the co-inhibitory molecules detected on TIL, immunohistochemistry
will be performed on residual formalin-fixed paraffin-embedded tumor tissue
that is regularly stored to identify the expression of the ligands of these
co-inhibitory molecules (for instance PDL1+2 and GAL9) on tumor (infiltrating)
cells.
Background summary
Rationale: Cholangiocarcinoma (CCA) is the most common primary malignancy of
the biliary tract, and is a cause of substantial morbidity and mortality.
Complete surgical resection is potentially curative, but it can only be
achieved in the 10% of patients who present with localized disease without
vascular invasion. Patients with locally advanced, metastatic, or recurrent
disease are typically offered chemotherapy and have a dismal prognosis.
Immunotherapy represents an attractive alternative treatment option, because it
is highly specific and can induce long-lasting immunological memory that may
permanently prevent tumor recurrence. It is our ultimate goal to design
effective immunotherapy for CCA patients. In the present study we aim to
identify targets for immunotherapy by focussing on the tumor-infiltrating
lymphocytes.
We hypothesise that co-stimulatory or -inhibitory molecules on the surface of T
cells can be targeted to affect T cell function as an immunotherapeutic
strategy to combat CCA.
Study objective
Objective: To determine which co-stimulatory and -inhibitory molecules are
expressed on tumor-infiltrating lymphocytes (TIL) derived from patients with
CCA, and to study the effects of targeting these molecules on their function in
ex vivo assays.
Study design
Study design: Cohort study in CCA-patients that are undergoing CCA resection in
our center. Tumor-infiltrating lymphocytes will be isolated from residual tumor
tissue and adjacent tumor-free liver tissue not needed for histological
evaluation (*rest materiaal*). Their phenotype will be evaluated by
flow-cytometry and their function, including effects of targeting
co-stimulatory and *inhibitory surface molecules, in cell culture experiments.
Blood is needed for comparison and to provide sufficient antigen presenting
cells for in vitro T-cell assays. In addition, leukocytes and plasma will be
stored frozen in a bio-bank for future studies.
Study burden and risks
Intervention: invasive measurement of 80 ml blood collected during surgery.
No benefit and negligible risk for the patients. Blood is taken once during
surgery and so no additional intervention is needed. Hopefully the results of
the study will benefit CCA-patients in the near future.
s Gravendijkwal 230 Room HA-212
Rotterdam 3015CE
NL
s Gravendijkwal 230 Room HA-212
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
Adult cholangiocarcinoma (CCA) patients that will undergo surgery for this disease.
Exclusion criteria
Patients who refuse blood donation/participation in the study
Patients with a severe immunocompromised condition, or patients taking immunosuppressive medication
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL57895.078.16 |