To study the frequencies and differentiation status of CD4 and CD8 T cell populations (Tnaive, TCM, TEM, TEMRA) in young (18-50) and old (>65) treatment naive metastasized melanoma patients at baseline and after treatment.
ID
Source
Brief title
Condition
- Skin neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To study the frequencies and differentiation status of CD4 and CD8 T cell
populations (Tnaive, TCM, TEM, TEMRA) in young (18-50) and old (> 65) treatment
naive metastasized melanoma patients at baseline and after treatment. In
addition, the frequencies and differentiation of Treg in these two age groups
will be assessed.
Secondary outcome
To study the presence of markers of the immune risk phenotype in patients (e.g.
CD4/CD8-ratio, CMV-status).
To study markers of immune senescence (e.g. CD27, CD28) and exhaustion (e.g.
PD1, CTLA-4).
Furthermore, this study increases our understanding of the pathophysiology of
behaviour and development of melanoma in elderly and young pateints.
Background summary
Age-related changes of the immune system may contribute to the development of
cancer in elderly. Longitudinal studies have identified an immune risk
phenotype (IRP) making elderly prone to both increased morbidity and mortality.
Recently a review came out by Akbar et al. that summarized the current
knowledge of immune senesence and immune exhaustion. They describe several
biochemical parameters that reflect the senescence of the immune system in
elderly patients (e.g. CD45RA, CD27, CD28, CCR7, CD57, PD1, CTLA4).
We know that the natural course of melanoma in old patients is unfavourable
compared to young patients, when classified for stage of disease. Age is an
independent factor of poor prognosis in melanoma. However, this needs to be
interpreted carefully and balanced. Presently it is not clear which
characteristics unique to the aging population, like the IRP and immune
senescence, play a major role in this observation.
We know that melanomas are highly immunogenic. This suggests that the natural
behavior of melanomas may depend on the functionality of the (aging) immune
system.
We hypothesize that aging of the immune system contributes to the development,
biological behaviour and worse outcome of melanomas in elderly.
Study objective
To study the frequencies and differentiation status of CD4 and CD8 T cell
populations (Tnaive, TCM, TEM, TEMRA) in young (18-50) and old (>65) treatment
naive metastasized melanoma patients at baseline and after treatment.
Study design
This will be an explorative study in patients with metastasized melanoma that
compares the status of the immune system in treatment naive patients between
young and old subjects and compare those date to the status of the immune
system of age- and sex-matched healthy controls. The data of those healthy
controls have already been collected from the Groningen Longevity cohort. We
will measure the baseline characteristics of the immune system (e.g. CD3, CD4,
CD8, CD25, CD27, CD28, CD31, CD45RO, CD45RA, CCR7, CMV, true count) in
treatment naive and treated metastasized melanoma patients.
Study burden and risks
All patients will receive standard diagnostic workup, treatment and follow up
for their metastasized melanoma. The burden lies solely in the extra blood
taken from patients who get a venapuncture for standard care at baseline and
after treatment
Hanzeplein 1 Hanzeplein1
Groningen 9713GZ
NL
Hanzeplein 1 Hanzeplein1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
> 18 years of age
informed consent
metastasized melanoma
After treatment
Exclusion criteria
severe anemia (Hb < 6.0)
concomitant chronic diseases that may affect immune system
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 | NL39173.042.11 |