Immune Checkpoints in Intraabdominal Ascites Fluid
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Case Advanced stage Colorectal cancer patients with intraabdominal ascites |
Diagnostic Test: Flow-cytometric analysis
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
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| Control Liver cirrhosis and congestive heart failure patients with intraabdominal ascites |
Diagnostic Test: Flow-cytometric analysis
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
|
Outcome Measures
Primary Outcome Measures
- Immune Checkpoint levels [4 months]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
- Advanced stage colorectal cancer patients with intraabdominal ascites
Exclusion Criteria:
-
Patients who have cancer other than colorectal cancer
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Patients with peritonitis
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Pregnant women
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HIV (+) patients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ufuk Oguz Idiz | Istanbul | Turkey | 34371 |
Sponsors and Collaborators
- Istanbul Training and Research Hospital
Investigators
- Principal Investigator: Ufuk Oguz Idiz, Assoc.Prof., Istanbul Training and Research Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- Nakano M, Ito M, Tanaka R, Yamaguchi K, Ariyama H, Mitsugi K, Yoshihiro T, Ohmura H, Tsuruta N, Hanamura F, Sagara K, Okumura Y, Nio K, Tsuchihashi K, Arita S, Kusaba H, Akashi K, Baba E. PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer. Cancer Sci. 2018 Sep;109(9):2986-2992. doi: 10.1111/cas.13723.
- Rådestad E, Klynning C, Stikvoort A, Mogensen O, Nava S, Magalhaes I, Uhlin M. Immune profiling and identification of prognostic immune-related risk factors in human ovarian cancer. Oncoimmunology. 2018 Nov 16;8(2):e1535730. doi: 10.1080/2162402X.2018.1535730. eCollection 2019.
- Yoshida N, Kinugasa T, Miyoshi H, Sato K, Yuge K, Ohchi T, Fujino S, Shiraiwa S, Katagiri M, Akagi Y, Ohshima K. A High RORγT/CD3 Ratio is a Strong Prognostic Factor for Postoperative Survival in Advanced Colorectal Cancer: Analysis of Helper T Cell Lymphocytes (Th1, Th2, Th17 and Regulatory T Cells). Ann Surg Oncol. 2016 Mar;23(3):919-27. doi: 10.1245/s10434-015-4923-3. Epub 2015 Nov 12.
- Colorectal Checkpoints