Our purpose is to establish whether the frequently observed absence of tumor regression in the presence of infiltrating T lymphocytes is due to a lack of T cell effector function or due to an inhibitory influence of the tumor microenvironment on T…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Skin neoplasms malignant and unspecified
- Pigmentation disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The presence of melanoma-reactive T lymphocytes will be determined in the tumor
tissue and in the blood of each patient. These T lymphocytes will subsequently
be tested for the ability to lyse melanoma cells in the metastasis and/or
melanocytes in the skin, using the skin/tumor explant system. The analyses in
this system also incorporate the influence of the tissue microenvironment on
the T cell functionality.
Secondary outcome
Our ex vivo in situ tumor and skin explant system is the first to integrate the
multidimensionality of human tumor-host interactions, and can therefore predict
the efficacy of these interactions in vivo more accurately than in vitro assays
based on rather artificial interactions between cells in suspension.
This study provides insight in the defects in individual patients that cause
failure of tumor regression by immunotherapy and may lead to novel strategies
to overcome these defects and improved immunotherapy of melanoma in the future.
Background summary
Melanoma is an immunogenic tumor that arises from the melanocytes and
occasionally triggers an immune response. Immune responses against melanoma can
also be actively induced in melanoma patients by immunotherapy. However, the
presence of an immune response against melanoma does not necesarily lead to
regression of the tumor.
Study objective
Our purpose is to establish whether the frequently observed absence of tumor
regression in the presence of infiltrating T lymphocytes is due to a lack of T
cell effector function or due to an inhibitory influence of the tumor
microenvironment on T cell-mediated lysis.
Study design
We have developed a skin/tumor explant system, in which the function of T
lymphocytes in the skin and in the tumor can be studied within the tissue
architecture. In this study we will compare the efficacy of T lymphocytes to
kill melanoma cells in the tumor or their efficacy to kill normal melanocytes
in the skin and cause depigmentation. T lymphoytes derived form both tumor
tissue and peripheral will be analyzed.
The experiments will address the following questions:
1. Are patient-derived T lymphocytes that are reactive with antigens on both
melanoma cells and melanocytes capable of killing melanoma cells in the tumor
tissue as well as melanocytes in the skin?
2. What is the influence of the tissue microenvironment on the functionality of
the
T lymphocytes?
3. What is the mechanism of cell death that is mediated by the T lymphocytes in
the tumor or skin tissue?
Study burden and risks
hardly or no burden for the patient and no additional risks
Plesmanlaan 121
1066 CX Amsterdam
NL
Plesmanlaan 121
1066 CX Amsterdam
NL
Listed location countries
Age
Inclusion criteria
Metastatic melanoma; (sub)cutaneous metastases
Exclusion criteria
Hemophilia en other blood coagulation disorders
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 | NL12654.031.06 |