Immune Checkpoints in Intraabdominal Ascites Fluid
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms; Ascites
Study type: Observational

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.
    

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.
    

Intervention name(s): Flow-cytometric analysis
Intervention type(s): Diagnostic Test
Intervention description(s): 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
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
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Keywords: Ascites; Immune checkpoints; Flow-cytometry