Mapping the peritoneal immune system to identify novel immunomodulatory treatment options for diseases with peritoneal involvement.

Peritoneal metastases (PM) are observed in 10-30% of patients with
gastrointestinal cancers, including colorectal and gastric cancer. The presence
of PM is associated with an extremely dismal prognosis, as patients typically
have limited responses to systemic therapy. In selected cases, highly invasive
cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy
(HIPEC) can still be performed, but also these procedures have limited survival
benefits and major comorbidity.
Because of the limited effective treatments for patients with peritoneal
metastases, it is imperative to find new treatment strategies. Among the
biggest breakthroughs in oncology in recent years has been the development of
immunotherapy: drugs that enhance the strength of immune system to attack tumor
cells. Immunotherapy has shown unprecedented durable responses even in
metastasized cancers and could therefore be an exciting new therapy for
patients with peritoneal metastasized cancer.
To understand how we can fully activate the immune system to fight peritoneal
metastatic cancers we first have to understand the cellular and phenotypical
characteristics of the peritoneal immune system in health and disease. Although
it is well known that many immune cells reside in the human peritoneal cavity,
the exact composition of the peritoneal immune system is unknown.
Interestingly, we recently discovered that in mice, the peritoneal immune
system is highly complex and consists of many subtypes of immune cells that had
not yet been characterized. Peritoneal immune cells had important functions in
protecting the host from excessive inflammation.
In this project, we will unravel the composition of the human peritoneal immune
system and study the differences in immune composition in peritoneal
metastasized cancers. This will advance our understanding on the role of the
peritoneal immune system in disease, with the overarching goal of finding novel
immunomodulatory treatment strategies.

Aim
The MAPS study aims to unravel the immune composition of the human peritoneal
cavity and the tumor immune environment in peritoneal metastasized gastric and
colorectal cancer. The overarching aim is to find new targets for immunotherapy
for this devastating disease.

Primary objectives:
To find new targets for immunotherapy for patients with peritoneal metastases,
our objectives of this study are:
1) Characterization of the different immune subsets in the human peritoneal
cavity
2) Identification of changes in immune subsets in patients with peritoneal
metastases as compared to patients without peritoneal involvement/metastases,
to identify novel immunotherapy targets.
3) Identification of changes in immune subsets in patients with inflammatory
bowel disease as compared to patients without peritoneal
involvement/inflammatory bowel disease to identify novel immunotherapy targets.

Longitudinal study

Since all patients are anesthetized and the abdomen needs to be entered for
surgery, the additional risk of this study is negligible. The peritoneal cavity
will be flushed with saline (0,9% NaCl) at body temperature. This fluid is used
in standard care during surgery and is deemed safe. The only differences with
standard care is that: 1) more fluid is used (approximately 1 liter of saline)
to collect as many cells as possible. 2) flushing of the abdomen occurs at the
start of the surgical procedure to minimize the contamination of blood immune
cells. One tube of maximum 10mL peripheral blood will be taken perioperative.
All patients have intravenous access during surgery, and there is no need for
additional venipuncture. There is no harm expected from the additional
collection of 10ml of blood, which is less than 0.2% of the patient*s blood
volume. If peritoneal metastasis of the primary tumor are present, a targeted
biopsy of these metastasis will be performed by the operating surgeon. If the
surgical resection specimen or a part of it is considered as 'waste' material,
we will sample the omentum with the milky spots for further analysis.

Benefit
There is no benefit for the patient that participates in this study.
Participation in this study will hopefully lead to new insights into the
composition of the human peritoneal immune system and new therapies for
patients with peritoneal metastases, a disease with dismal prognosis. This will
be of importance for future patients with peritoneal metastasized cancer, and
potentially also for patients with peritoneal involvement in other diseases.