Immune Checkpoints in Intraabdominal Ascites Fluid

• ClinicalTrials.gov Identifier: NCT04540159
• Recruitment Status: Recruiting
• First Posted: September 7, 2020
• Last Update Posted: July 27, 2021
• Sponsor: Istanbul Training and Research Hospital
• Information provided by (Responsible Party): Ufuk Oguz Idiz, Istanbul Training and Research Hospital

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
Colorectal Cancer	Diagnostic Test: Flow-cytometric analysis

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

• Study Type: Observational
• Estimated Enrollment: 80 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Measurement of Immune Checkpoints in Intraabdominal Ascites Fluid in Patients With Advanced Colorectal Cancer
• Actual Study Start Date: January 1, 2021
• Estimated Primary Completion Date: September 1, 2021
• Estimated Study Completion Date: November 1, 2021

Groups and Cohorts

Group/Cohort	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
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 :

1. Immune Checkpoint levels [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

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Criteria

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

Contacts and Locations

Contacts

Contact: Ufuk Oguz Idiz, Assoc.Prof.; 905062044714; oguzidiz@yahoo.com

Locations

Turkey

Ufuk Oguz Idiz; Recruiting

Istanbul, Turkey, 34371

Contact: Ufuk Oguz Idiz, Assoc. Prof. +905062044714 oguzidiz@yahoo.com

Sponsors and Collaborators

Istanbul Training and Research Hospital

Investigators

• Principal Investigator: Ufuk Oguz Idiz, Assoc.Prof.; Istanbul Training and Research Hospital

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.

• Responsible Party: Ufuk Oguz Idiz, Assoc. Prof. MD, Istanbul Training and Research Hospital
• ClinicalTrials.gov Identifier: NCT04540159
• Other Study ID Numbers: Colorectal Checkpoints
• First Posted: September 7, 2020
• Last Update Posted: July 27, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ufuk Oguz Idiz, Istanbul Training and Research Hospital:

Ascites; Immune checkpoints; Flow-cytometry

Additional relevant MeSH terms:

Colorectal Neoplasms; Ascites; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pathologic Processes