The Status of Immune Checkpoints at Gastrointestinal Cancer

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.

Inclusion criteria

• Patients with intraabdominal ascites with benign reasons (liver cirrhosis, Congestive heart failure, etc.) for control group
• Patients with advanced stage colorectal cancer, gastric cancer and pancreatic cancer who develop malignant ascites for gastrointestinal cancer group

Exclusion criteria

• Pregnant
• Primary immune system failure
• HIV patients