To determine which costimulatory and co-inhibitory molecules are expressed on tumor-infiltrating lymphocytes (TIL) derived from patients with HCC or 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 numbers of different lymphocyte populations that
together compose the tumor-infiltrating lymphocyte pool
2) Expression of costimulatory and co-inhibitory molecules on TIL versus
lymphocytes isolated from tumor-free tissue versus circulating lymphocytes
3) Effect of blocking co-inhibitory molecules or stimulating costimulatory
molecules expressed by TIL on their function (proliferation and cytokine
production) in ex vivo 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 (e.g. PDL-1+2, GAL-9) on tumor (infiltrating) cells.
Background summary
Liver cancer is the second most common cause of cancer-related mortality
worldwide. The most prevalent primary liver cancer is hepatocellular carcinoma
(HCC), followed by cholangiocarcinoma (CCA). The current treatment options for
HCC and CCA are only curative for patients with early disease. Unfortunately,
the majority of HCC and CCA patients are not eligible for curative procedures
because of late diagnosis and thus have poor 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 HCC and CCA patients. In the present study we aim
to identify targets for immunotherapy by focusing on the tumor-infiltrating
lymphocytes.
We hypothesize that costimulatory or co-inhibitory molecules on the surface of
lymphocytes can be targeted to affect lymphocyte function (a.o. T cell) as an
immunotherapeutic strategy to combat HCC and CCA.
Study objective
To determine which costimulatory and co-inhibitory molecules are expressed on
tumor-infiltrating lymphocytes (TIL) derived from patients with HCC or CCA, and
to study the effects of targeting these molecules on their function in ex vivo
assays.
Study design
Cohort study in HCC or CCA patients in our centers that are undergoing
resection. Tumor-infiltrating lymphocytes will be isolated from residual tumor
tissue and adjacent tumor-free tissue not needed for histological evaluation
(*restmateriaal*). Their phenotype will be evaluated by flow cytometry and
their function, including effects of targeting costimulatory and co-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 in a biobank for future
studies.
Study burden and risks
Intervention: invasive measurement of 80 mL of blood collected during surgery.
No benefit and negligible risk for the patients. Blood is taking once during
surgery and so no additional intervention is needed. Hopefully, the results of
the study will benefit HCC and CCA patients in the near future.
's Gravendijkwal 230
Rotterdam 3015CE
NL
's Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
Adult hepatocellular carcinoma (HCC) or 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 | NL58958.018.17 |