T Helper Cytokines in End Stage Colorectal Cancers

Evaluation of T Helper Cytokines in Intraabdominal Ascites in End Stage Colorectal Cancers

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. Differentiation of T cells towards Th2 and regulatory T cells is also reported to be effective in tumor progression.

Among the mechanisms of escape from the immune system, changes in the tumor microenvironment play an important role. The role of regulatory T lymphocytes, a subgroup of T cells that play a regulatory role by suppressing the function of other T lymphocytes, is to reduce the chronic immune response against viruses, tumors and patients's own antigens. The common feature of all Tregs is that they secrete one or more anti-inflammatory molecules such as IL-10, TGFβ or IL-35. High levels of Tregs have been found in peripheral blood, tumor tissue and lymph nodes in patients with malignancy.

In our study, it is aimed to evaluate whether there is a difference in intraabdominal ascites fluid T helper cytokine levels in patients with end-stage colorectal cancers compared to patients without malignancy.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Diagnostic test: Flow-Cytometric analysis

Detailed Description

Colorectal cancers are the third most common type of cancer in the world. Peritoneal carcinomatosis and intraabdominal ascites 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. Differentiation of T cells towards Th2 and regulatory T cells is also reported to be effective in tumor progression.

Among the mechanisms of escape from the immune system, changes in the tumor microenvironment play an important role. The role of regulatory T lymphocytes, a subgroup of T cells that play a regulatory role by suppressing the function of other T lymphocytes, is to reduce the chronic immune response against viruses, tumors and patient's own antigens. The common feature of all Tregs is that they secrete one or more anti-inflammatory molecules such as IL-10, TGFβ or IL-35. High levels of Tregs have been found in peripheral blood, tumor tissue and lymph nodes in patients with malignancy.

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.

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 cytokine level in patients with end-stage colorectal patients compared to patients without malignancy.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34371
    • Ufuk Oguz Idiz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The end stage colorectal cancer patients with intraabdominal ascites will be the case group.

Also congestive heart failure and liver cirrhosis patients with intraabdominal ascites will be the control group

Description

Inclusion Criteria:

• End stage Colorectal Cancer patients

Exclusion Criteria:

• Another synchronous tumor with colorectal cancer
• HIV patients
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case; End Stage Colorectal Cancer patients with intraabdominal ascites	Diagnostic test: Flow-Cytometric analysis; IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 22, IFN-γ and TNF-α levels in the intraabdominal ascites
Control; Congestive heart failure and liver cirrhosis patient who had intraabdominal ascites	Diagnostic test: Flow-Cytometric analysis; IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 22, IFN-γ and TNF-α levels in the intraabdominal ascites

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cytokine levels	IL-2, 4, 5, 6, 9, 10, 13, 17A, 17F, 22, IFN-γ and TNF-α levels	3 months

Collaborators and Investigators

• Sponsor: Istanbul Training and Research Hospital

Publications and helpful links

General 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.
• 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.
• Syed Khaja AS, Toor SM, El Salhat H, Ali BR, Elkord E. Intratumoral FoxP3+Helios+ Regulatory T Cells Upregulating Immunosuppressive Molecules Are Expanded in Human Colorectal Cancer. Front Immunol. 2017 May 26;8:619. doi: 10.3389/fimmu.2017.00619. eCollection 2017.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 15, 2020

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 25, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Cytokine; Ascites; Flow-cytometry; T cell
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: Colorectal cytokine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No