Immune Checkpoints in Intraabdominal Ascites Fluid

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04540159
• Other study ID #: Colorectal Checkpoints
• Status: Completed
• Start date: January 1, 2022
• Est. completion date: December 1, 2022

Study information

• Verified date: December 2022
• Source: Istanbul Training and Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 1, 2022
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Ascites
• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Diagnostic Test:
• Flow-cytometric analysis
Measuring the level of sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-ß1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9 in the intraabdominal ascites

Locations

Country	Name	City	State
Turkey	Ufuk Oguz Idiz	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Istanbul Training and Research Hospital

Country where clinical trial is conducted

Turkey, 

References & Publications (3)

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. — View Citation

Radestad 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. — View Citation

Yoshida N, Kinugasa T, Miyoshi H, Sato K, Yuge K, Ohchi T, Fujino S, Shiraiwa S, Katagiri M, Akagi Y, Ohshima K. A High RORgammaT/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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immune Checkpoint levels	Measuring the level of sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-ß1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9 in the intraabdominal ascites	4 months