Clinical trial NCT04540146: T Helper Cytokines in End Stage Colorectal Cancers
Official title: Evaluation of T Helper Cytokines in Intraabdominal Ascites in End Stage Colorectal Cancers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Colorectal Cancer
Keywords: Ascites
T cell
Flow-cytometry
Cytokine
Lead sponsor: Istanbul Training and Research Hospital
Sponsor class: OTHER_GOV
First posted: 2020-09-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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. 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.

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.

Eligibility criteria: Inclusion Criteria:

* End stage Colorectal Cancer patients

Exclusion Criteria:

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

Primary outcomes:
measure: cytokine levels
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Ufuk Oguz Idiz
Study officials:
affiliation: Istanbul Training and Research Hospital
name: Ufuk Oguz Idiz, Assoc.Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
citation: 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.