Characterize the tumor immune microenvironment (TiME) in head and neck squamous cell carcinoma (HNSCC). Specifically we want to understand which molecular and/or immunological mechanisms are different between different genetic subgroups of HNSCC (i.…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this study is to define the TiME in the various
anatomical and molecular HNSCC subclasses (HPV-related, non-HPV related
CNA-other and non-HPV related CNA-quiet) and to comprehend which molecular
and/or immune mechanisms relate with prognosis and response to therapies.
Differences in the TiME will be assessed by flow cytometry, multiplexed
immunohistochemistry, DNA/RNA sequencing, spatial transcriptomics, primary
tumor cultures and functional immune assays.
Secondary outcome
Secondary endpoints in our study will be TiME characteristics which are related
to:
1. Immunotherapy response
2. Clinical outcome / overall survival
3. New immune suppressive mechanisms in HNSCC
Background summary
Head and neck squamous cell carcinoma (HNSCC) arises in the mucosal linings of
the upper aerodigestive tract. Common risk factors are alcohol and tobacco use,
genetic predisposition and human papillomavirus (HPV) infection. Patients
generally have a poor prognosis and the survival rate has improved minimally
during the past years. Recently, immunotherapy has been approved for the
treatment of patients with recurrent or metastatic HNSCC and caused the first
breakthrough in HNSCC treatment in decades. In addition, application as
neoadjuvant treatment prior to or as substitute of surgery are underway.
However, current immunotherapy is only effective in about 20% of patients and
the reason why the majority of patients do not respond to immunotherapy is
unclear. Extensive immunological and molecular characterization of the tumor
immune microenvironment (TiME) in HNSCC is warranted to elucidate suppressive
mechanisms that may hamper the effectiveness of immunotherapy.
Over the past decades it has been appreciated that HPV-related HNSCC have a
better prognosis and respond better to standard-of-care treatment. Also
immunotherapy seems to work better in a subset of these patients. More
recently, we and others, have identified that among the non-HPV-related tumors,
there are tumors that show many chromosomal aberrations (CNA-other), whereas a
smaller subgroup (<10%) has no or only few chromosomal aberrations (CNA-quiet).
While we have shown in a retrospective cohort that the latter group has a
better prognosis, the mechanisms behind this are not understood. With the
current project we aim to identify these mechanisms, and whether they are
molecular, or immunological and whether they are related to response to
treatment.
Study objective
Characterize the tumor immune microenvironment (TiME) in head and neck squamous
cell carcinoma (HNSCC). Specifically we want to understand which molecular
and/or immunological mechanisms are different between different genetic
subgroups of HNSCC (i.e. HPV-related, non-HPV related with many chromosomal
abberations, and non-HPV related with few to no chromosomal abberations) and
between HNSCC that develop at different anatomical sites within the head and
neck area. We want to know how this is related to response to treatment.
Study design
A longitudinal study in which tumor and blood of a consecutive patient cohort
and the clinical information regarding this material will be collected.
Study burden and risks
We anticipate limited burden and risks associated with participation. Tissue
biopsies will be obtained during the diagnostic surgery under full anesthesia.
The participants may experience some pain at the site of the biopsy. For the
additional blood draw for research, a vene puncture will be performed. This may
give mild irritation or bruising at the injection site.
The participants themselves will not benefit from participating in this study.
We anticipate that the results from this study will help us identify novel
immune suppressive pathways in head and neck cancer that could lead to
development of novel treatment modalities. Also, the study may reveal
informative biomarkers that may help in selecting those patients who are like
to benefit from (immuno)therapy strategies and/or those who are unlikely to
respond.
De Boelelaan 1118
Amsterdam 1081 HV
NL
De Boelelaan 1118
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
1. Patients are scheduled for panendoscopy or surgery for squamous cell
carcinoma of the oral cavity, oropharynx, hypopharynx, larynx or cervical part
of oesophagus.
2. Patients must have sufficient knowledge of the Dutch language to understand
the meaning of the study as described in the patient information.
3. Patients must have the mental capacity to understand the meaning of the
study as described in the patient information.
4. Patients must give written informed consent.
5. Age of the patients should be >18. An upper limit of age will not be
applied. Elderly patients who are fit enough to undergo surgery in the head and
neck area are not likely to encounter negative effects of the extra procedures
that will be applied as part of the study.
Exclusion criteria
Too limited size of the carcinoma according to the treating physician.
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 | NL86264.018.24 |