Immune Checkpoints in Intraabdominal Ascites Fluid

Study Overview
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Brief Summary
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Colorectal cancers are the third most common type of cancer in the world. Peritoneal carcinomatosis and intraabdominal acid development occur in advanced stages of colorectal cancers. It is known that the immune system plays an important role in tumor development or tumor eradication. Among the mechanisms of escape from the immune system, changes in the tumor microenvironment play an important role. Immune checkpoints are molecules that have become popular especially after the Nobel Prize in 2018, and are important in revealing the relationship between cancer and the immune system. In our study, it is aimed to evaluate whether there is a difference in intraabdominal ascites fluid immune checkpoints level in patients with advanced colorectal cancer patients compared to patients without malignancy.

Detailed Description
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Colorectal cancers are the third most common type of cancer in the world. Peritoneal carcinomatosis and intraabdominal acid development occur in advanced stages of colorectal cancers. It is known that the immune system plays an important role in tumor development or tumor eradication. The role of the immune system in colorectal cancers has been demonstrated with the effects of tumor-infiltrating lymphocytes (TIL) and immune control points on TILs or immune control point ligands on patient survival, especially in recent studies. Studies in the literature usually include immunological examinations of patient blood or tumor tissue. Immune checkpoints are molecules that have become popular especially after the Nobel Prize in 2018, and are important in revealing the relationship between cancer and the immune system. Programmed Cell Death Protein-1 (PD-1) and its ligand, PD-L1, is an immune checkpoint that acts by blocking T cell receptor signal transduction and auxiliary stimuli. T cell immunoglobulin and mucin domain 3 (TIM-3) are mostly expressed on T cells, Tregs, dendritic cells, B cells, macrophages, natural killer cells (NK) and mast cells that produce interferon-(10). Impairment in regulation of TIM-3 expression has been associated with autoimmune diseases. High TIM-3 expression is associated with suppression of T cell responses and T cell depletion, which is characterized by loss of T cell functions during chronic viral infections and during tumor development. With the clinical success of immune checkpoint inhibitors such as ipilimumab and nivolumab for melanoma and lung cancer, immune checkpoints have attracted more attention. There are many publications in the literature evaluating immunological markers from ascites fluid samples for various reasons. In these studies, T and B cell subtypes were examined from ascites fluid samples taken from patients with ascites, especially ovarian cancer and liver cirrhosis. In the only study on gastrointestinal cancers, immunophenotyping was performed in intraabdominal ascites and blood in 22 advanced gastrointestinal tumor patients and some cell subgroups were associated with worse clinical outcome. In the literature, there is no study on cytokine analysis from intra-abdominal ascites fluids specific to colorectal cancer. In our study, it is aimed to evaluate whether there is a difference in intraabdominal ascites fluid immune checkpoints level in patients with advanced colorectal cancer patients compared to patients without malignancy.

Official Title
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Measurement of Immune Checkpoints in Intraabdominal Ascites Fluid in Patients With Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Diagnostic Test: Flow-cytometric analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced stage colorectal cancer patients with intraabdominal ascites Exclusion Criteria: Patients who have cancer other than colorectal cancer Patients with peritonitis Pregnant women HIV (+) patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case<br>Advanced stage Colorectal cancer patients with intraabdominal ascites | Diagnostic Test: Flow-cytometric analysis<br>* Measuring the level of sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9 in the intraabdominal ascites<br>|
| Control<br>Liver cirrhosis and congestive heart failure patients with intraabdominal ascites | Diagnostic Test: Flow-cytometric analysis<br>* Measuring the level of sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9 in the intraabdominal ascites<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Checkpoint levels | Measuring the level of sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9 in the intraabdominal ascites | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ascites, Immune checkpoints, Flow-cytometry