Investigate the phenotype, function and regulation of TRM in healthy human lung tissue, lung tumors and peripheral blood to improve the understanding of respiratory diseases and adoptive T-cell therapy for lung cancer.
ID
Source
Brief title
Condition
- Other condition
- Respiratory tract neoplasms
Synonym
Health condition
general principles of respiratory tract disorders including infections and neoplasms
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Which regulatory circuits modulate T-cell phenotype and function in healthy
human lung tissue, lung tumors and peripheral blood
Secondary outcome
To answer the primary objective we want to perform the following analyses:
1) Optimization of the isolation of T-cells from tumor and lung tissue
(enzymatic digestion, collagenases, mechanical force).
2) Phenotypic comparison of T-cells derived from healthy lung tissue, lung
tumors and peripheral blood using multiparameter flow cytometry.
3) Investigation of the localisation of T-cells in healthy lung tissue and lung
tumors as well as their accessory cells using confocal microscopy.
4) Investigation of response of lung TRM and T-cells derived from tumor tissue
and peripheral blood to activating stimuli (antigen specific/non-specific
T-cell receptor stimulation, costimulation and cytokines) to analyse their
differential effector functions.
5) Comparison of the transcriptome and clonal composition (both genome wide and
T-cell receptor (TCR) sequence) of paired TRM, tumor and peripheral blood
derived T-cell populations.
6) Comparison of the proteome of paired TRM, tumor and peripheral blood derived
T-cell populations.
7) Combined analyses of the proteomes with the transcriptomes to reveal the
proteins that are regulated in a post-transcriptional manner.
Background summary
The lungs are the largest interphase between the body and the environment and
are constantly engaged by inhaled pathogens. This makes the respiratory tract a
prime site for the occurrence of infections and cancer and warrants the
necessity of an active immunological defence. At the same time aberrant immune
activation needs to be avoided to prevent collateral damage of the vital lung
tissue. A delicate balance between protection and immunopathology needs to be
maintained as dysregulation contributes to asthma, allergy and other lung
diseases. Emerging evidence suggests that the recently described subset of
resident memory T-cells (TRM), located in a variety of barrier tissues,
mediates optimal protective immunity in the lungs. Little is known about how
these cells are regulated, interact with other immunological subsets and
contribute to inflammatory and autoimmune diseases.
Study objective
Investigate the phenotype, function and regulation of TRM in healthy human lung
tissue, lung tumors and peripheral blood to improve the understanding of
respiratory diseases and adoptive T-cell therapy for lung cancer.
Study design
This cross-sectional observational study involves an in-depth characterization
of lung T-cell subsets and interacting immunological subsets. Gained insights
will lead to further experimental investigation with the objective to study
lung TRM regulation.
Study burden and risks
The participants of this study are, asked about their health history and
smoking habits in case these are not already documented by the attending
physician upon admission. Additionally the participants undergo a one-time
blood draw of 50ml from an existing intra-vascular catheter during the
scheduled surgery. This does not cause any additional discomfort to the
patient. The risks of this routine procedure are minimal and the withdrawal of
such small volumes of blood is generally well tolerated. The participants do
not benefit from the participation in this study. However, basic insights into
immune responses in the healthy lungs and tumor microenvironment may lead to
improved therapies against respiratory infections and lung tumors in the
future.
Plesmanlaan 125
Amsterdam 1066 CX
NL
Plesmanlaan 125
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Adult (18+)
- Undergoing lobectomy or pneumectomy for an isolated primary lung tumor
- Undergoing lung tissue resection for a primary non-infectious pulmonary or pleural disease
Exclusion criteria
- Previous radiotherapy in which the lungs might have been directly in the radiation field
- Chemotherapy in the last 6 months
- Sleeve lobectomy, wedge resection or metastasectomy
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 | NL52453.100.15 |