The Status of Immune Checkpoints at Gastrointestinal Cancer
Condition: Gastrointestinal Cancer
MeSH terms: Gastrointestinal Neoplasms
Study type: Observational

Summary: 
      Colorectal cancers are the third most common cancer in the world. In advanced stages of
      colorectal cancers, peritoneal carcinomatosis and intraabdominal acid development occur.
      Although stomach cancer is the 5th most common cancer in the world, it is the third cancer
      with the highest mortality. Pancreatic cancer is one of the highest mortality cancers
      worldwide. Likewise, in advanced stages of stomach and pancreatic cancer, peritoneal
      carcinomatosis and intra- abdominal acid development occur. It is known that the immune
      system plays an important role in tumor development or destruction of tumor. Recent studies
      have shown that tumor cells develop escape mechanisms in the tumor microenvironment to escape
      from host immunity. It has been reported that differentiation of T cells towards Th2 and
      regulatory T cells is also effective in tumor progression(6). Changes in the tumor
      microenvironment and immune checkpoints are important mechanisms that lead to escape from the
      immune system. Immune checkpoints are on the agenda especially after 2018 Nobel Prize and
      they are important molecules in revealing the relationship.In our study, it is aimed to
      evaluate whether there is a difference in immune control points in patients with end-stage
      colorectal cancer, gastric cancer and pancreatic cancer compared to patients without
      malignancy, and the relationship of these parameters with patient survival and tumor spread
      mechanisms.
    

Detailed description: 
      Colorectal cancers are the third most common cancer in the world. In advanced stages of
      colorectal cancers, peritoneal carcinomatosis and intraabdominal acid development occur.
      Although stomach cancer is the 5th most common cancer in the world, it is the third cancer
      with the highest mortality. Pancreatic cancer is one of the highest mortality cancers
      worldwide. Likewise, in advanced stages of stomach and pancreatic cancer, peritoneal
      carcinomatosis and intra- abdominal acid development occur. It is known that the immune
      system plays an important role in tumor development or destruction of tumor. Recent studies
      have shown that tumor cells develop escape mechanisms in the tumor microenvironment to escape
      from host immunity. It has been reported that differentiation of T cells towards Th2 and
      regulatory T cells is also effective in tumor progression(6). Changes in the tumor
      microenvironment and immune checkpoints are important mechanisms that lead to escape from the
      immune system. Immune checkpoints are on the agenda especially after 2018 Nobel Prize and
      they are important molecules in revealing the relationship.

      Programmed Cell Death Protein-1 (PD-1) and its ligand, PD-L1, is an immune control point that
      acts by blocking T cell receptor signal transduction and co-stimuli. T cell immunoglobulin
      and mucin domain 3 (TIM-3) are mostly expressed on interferon-gamma-producing T cells, Tregs,
      dendritic cells, B cells, macrophages, natural killer cells (NK) and mast cells. Enhanced
      regulation of TIM-3 expression is associated with autoimmune diseases. High TIM-3 expression
      is associated with suppression of T cell responses and T cell depletion 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 received more attention.

      The role of the immune system in colorectal cancers has been demonstrated, especially in
      recent studies, with the effects of tumor-infiltrating lymphocytes (TIL) and immune control
      points on TILs or immune control point ligands on patient survival. Studies in the literature
      usually include immunological examinations of patient blood or tumor tissue.

      There are many publications in the literature on the study of immunological markers from acid
      fluid samples for various reasons. In these studies, T and B cell subtypes were examined from
      acid fluids samples taken from patients with spontaneous ascites, especially ovarian cancer
      and liver cirrhosis. In the only study conducted on gastrointestinal cancers,
      immunophenotyping was performed in intraabdominal ascites and blood in 22 advanced
      gastrointestinal tumor patients, and some cell subgroups were associated with clinical
      worsening.

      In the literature, there is no study on immune control points from intra-abdominal acid
      fluids specific to gastric and colorectal cancer. In our study, it is aimed to evaluate
      whether there is a difference in immune control points in patients with end-stage colorectal
      cancer, gastric cancer and pancreatic cancer compared to patients without malignancy, and the
      relationship of these parameters with patient survival and tumor spread mechanisms.
    

Intervention name(s): Flow cytometric analysis
Intervention type(s): Diagnostic Test
Intervention description(s): Measuring the sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9 levels with flow cytometry
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with intraabdominal ascites with benign reasons (liver cirrhosis, Congestive heart
        failure, etc.) will be the control group, and patients with advanced stage colorectal
        cancer, gastric cancer and pancreatic cancer who develop malignant ascites will be the
        gastrointestinal cancer group
      
Keywords: Pancreatic cancer; Gastric cancer; Colorectal Cancer; Immune checkpoints