Neoplasms

Digestive System Diseases

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Stomach Neoplasms

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Cancer

Pancreatic Cancer

Hematinics

All Drugs and Chemicals

Liver Extracts

Patients with advanced stage colorectal cancer, gastric cancer and pancreatic cancer who develop malignant ascites

Patients with intraabdominal ascites with benign reasons (liver cirrhosis, Congestive heart failure, etc.) .

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

Flow cytometric analysis

Ufuk Oguz Idiz, Assoc. Prof. MD.

Eyup Kaya, MD

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.

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.

The Status of Immune Checkpoints at Gastrointestinal Cancer

Determination of Immune Check Point Levels in Paracentesis Samples of Gastrointestinal System Malignancy Cases

sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9

Prof. Dr. Cemil Tascıoglu Education and Research Hospital Organization

Istanbul Training and Research Hospital

M.D. PhD

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Stage II-III rectal cancer patients who have neoadjuvant therapy

The measurement of soluble immune checkpoints of stage II-III rectal cancer before neoadjuvant treatment

Immune checkpoint measure

Ufuk Oguz Idiz, Assoc.Prof.

Colorectal cancer is the third most frequently diagnosed type of cancer in the world. Recent developments in the treatment of cancers suggest that immune checkpoint inhibitors will play an important role. Many studies have documented many types of soluble receptors and ligands that can be detected in plasma in cancer, and plasma levels of these molecules correlate with cancer severity. There is only one study in the literature evaluating the status of soluble immune control points in patients with rectal cancer. The aim of this study is to investigate the role of serum immune checkpoints before neoadjuvant therapy in predicting clinical response in patients with rectal cancer. In this way, it is aimed to show whether immune checkpoints are predictive markers that can predict response to neoadjuvant therapy in patients with stage II-III rectal cancer.

Colorectal cancers are the third most frequently diagnosed cancer type in the world. Recent developments in the treatment of cancers suggest that immune checkpoint inhibitors will play an important role. Among the different immune checkpoint treatments, those containing PD-1 and CTLA-4 stand out as the most effective ones. In clinical trials, anti-CTLA-4 antibody and anti-PD-1 antibody showed great promise by significantly improving overall survival in newly diagnosed and patients who had neoadjuvant treatment against a wide range of solid and hematological malignancies. However, the effects of soluble receptors and ligands on immune system regulation and cancer therapy have been less studied. Soluble receptors and ligands, which are part of a family that includes full-length receptors and ligands, are produced by mRNA expression or cleavage of membrane-bound proteins and are found free in plasma. These structures may play important roles in immune system regulation through interactions between soluble receptors and full-length ligands or between soluble ligands and full-length receptors. Many studies have documented many types of soluble receptors and ligands that can be detected in plasma in cancer patients, and plasma levels of these molecules correlate with cancer severity. As soluble molecules, serum and tissue levels can be easily detected. These molecules are also critical factors for assessing the severity and prognosis of cancer and many other diseases.

In a study, the amounts of PD-L1 and CTLA-4 both on the tumor and soluble in the blood were evaluated, and the high levels of PD-L1 and CTLA-4 were associated with a poor prognosis.

There is only one study in the literature evaluating the status of soluble immune control points in patients with rectal cancer. Of many immune control points, only PD-1 and PD-L1 were evaluated in this study.

In this study, it is planned to include patients who were diagnosed with stage II-III rectal cancer in the General Surgery outpatient clinic of Istanbul Training and Research Hospital between May 2022 and October 2022 and required neoadjuvant treatment in their examinations. Routine rectal cancer surgery will be performed after neoadjuvant treatment of the patients included in the study, and their pathology reports will be examined, and tumor regression scores will be evaluated. Before neoadjuvant treatment, 10 cc of blood will be collected from the patients in a biochemistry tube, their serum will be separated by centrifugation and stored in a -80oC refrigerator. After the collection of all samples, serum immune control points will be evaluated by flow cytometry from the samples.

Thus, it will be determined whether there is any relationship between serum immune checkpoint levels and tumor regression score.

Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer

Role of Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer Patients

Assoc. Prof. MD. PhD

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Immune Checkpoint Inhibitors

Immunosuppressive Agents

* Baseline
* Week 6 Day 1
* Week 12 Day 1

If feasible, an optional tumor biopsy specimen will be collected during baseline visit for a maximum of 30 patients included in IUCT-O center.

Blood samples will be collected at different time points:

This trial is a translational proof-of-concept, open-label, prospective cohort study of 60 patients aiming to identify the clinical markers and/or biomarkers associated with therapeutic response to immune checkpoints inhibitors, in patients with advanced melanoma.

The study will be conducted on a population of patients treated with anti-PD-1 alone (nivolumab or pembrolizumab) or in combination (nivolumab + ipilimumab) in the context of routine care.

For each included patient, blood samples will be collected at different time points.

If feasible, an optional tumor biopsy specimen will be collected during baseline visit.

All included patients will be followed-up for tumor response and toxicity until Week 12.

After Week 12, survival data (tumor status and/or survival status) will be collected every 3 months until a maximum duration of 1 year from the first study dose.

Evaluation of Sphingolipids as Predictive Biomarkers of Immune Checkpoint Inhibitor Response in Melanoma Patients

Institut Claudius Regaud

Symptoms and General Pathology

Ascites

Colonic Diseases

Advanced stage Colorectal cancer patients with intraabdominal ascites

Liver cirrhosis and congestive heart failure patients with intraabdominal ascites

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

Flow-cytometric analysis

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.

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.

Immune Checkpoints in Intraabdominal Ascites Fluid

Measurement of Immune Checkpoints in Intraabdominal Ascites Fluid in Patients With Advanced Colorectal Cancer

Assoc. Prof. MD

Breast Neoplasms

Breast Diseases

The breast cancer patients with no response to neoadjuvant therapy

The breast cancer patients with moderate response to neoadjuvant therapy

The breast cancer patients with good response to neoadjuvant therapy

Measurement 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

Immune checkpoint measurement

Ufuk Oguz Idiz, Assoc. Prof

Breast cancer is the most common type of cancer in women and the second most common cause of death after lung cancer. In epidemiological studies, its prevalence is 22-26%, and the mortality risk due to breast cancer is around 18%.

It is known that the immune system has an important role in tumor development or tumor destruction. Recent studies have shown that tumor cells acquire escape mechanisms to escape host immunity in the tumor microenvironment.

Studies have reported that immune checkpoints are elevated in many types of cancer and have a poor prognosis. Up or down regulation of immune checkpoints is observed to protect breast cancer cells from the anti-tumor responses of the immune system. There are also immune checkpoints found in plasma in soluble form, and the number of studies evaluating soluble immune checkpoints in cancers is very limited in the literature. Measurement of soluble immune control points is easier than those expressed on the surface, and many markers can be evaluated at the same time. There are very few studies in the literature evaluating soluble immune checkpoints in breast cancer.

The aim of this study is to investigate the role of soluble immune checkpoints in predicting the response to neoadjuvant therapy in locally advanced breast cancers.

Breast cancer is the most common type of cancer in women and the second most common cause of death after lung cancer. In epidemiological studies, its prevalence is 22-26%, and the mortality risk due to breast cancer is around 18%. While the classification of malignant breast tumors has traditionally been made according to their histological appearance, some subtypes have been defined according to their molecular features. The different behavior of tumors in the luminal group led to the need to divide this group into subtypes as luminal A and B. The luminal group A, which has the highest prevalence among breast cancers; It includes Her2-negative tumors with low proliferative activity, low mitotic rate and histological grade. The prognosis of patients with luminal A tumors is very good and metastases are mostly limited to bones. Luminal-B tumors have a more aggressive course. The most important difference of this group is that tumors have a high proliferation rate. The breakpoint between luminal A and B is generally accepted as less than 14% of tumor cells showing nuclear Ki67 expression immunohistochemically. In addition, approximately 30% of Her2-positive tumors are immunohistochemically in the luminal B phenotype.

It is known that the immune system has an important role in tumor development or tumor destruction. Recent studies have shown that tumor cells acquire escape mechanisms to escape host immunity in the tumor microenvironment.

Immune checkpoints are important molecules that are on the agenda especially after receiving the Nobel Prize in 2018 and in revealing the relationship between cancer and the immune system. Programmed Cell Death Protein-1 (PD-1) and its ligand, PD-L1, are immune checkpoints that act by inhibiting T cell receptor signal transmission and auxiliary stimuli. T cell immunoglobulin and mucin domain 3 (TIM-3) are mostly expressed on interferon-γ producing T cells, Tregs, dendritic cells, B cells, macrophages, natural killer cells (NK) and mast cells.

Studies have reported that immune checkpoints are elevated in many types of cancer and have a poor prognosis. Up or down regulation of immune checkpoints is observed to protect breast cancer cells from the anti-tumor responses of the immune system. Although many studies have been conducted on immune checkpoints in recent years, a limited number of immune checkpoints which are expressed on the cell surface have been evaluated in each study. There are also immune checkpoints found in plasma in soluble form, and the number of studies evaluating soluble immune checkpoints in cancers is very limited in the literature. Measurement of soluble immune control points is easier than those expressed on the surface, and many markers can be evaluated at the same time. There are very few studies in the literature evaluating soluble immune checkpoints in breast cancer.

The aim of this study is to investigate the role of soluble immune checkpoints in predicting the response to neoadjuvant therapy in locally advanced breast cancers.

Evaluation of the Role of Immune Checkpoints in Response to Breast Cancer Neoadjuvant Therapy

Evaluation of the Role of Immune Checkpoints in Response to Breast Cancer Neoadjuvant

Values in pg/ml of sCD25 (IL-2Ra), 4-1BB, CD27, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-L2, PD-1, Tim-3, LAG-3, Galectin-9

Pembrolizumab

Immunomodulating Agents

Nivolumab

Ipilimumab

Patients treated with anti-PD-1 alone (nivolumab or pembrolizumab)

Patients treated with the combined treatment anti-PD-1+anti-CTLA-4 (nivolumab + ipilimumab)

Tumor biopsy specimens (if feasible) and blood samples will be collected at Baseline, Week 6 Day 1 (blood sample only) and Week 12 Day 1.

Tumor biopsy specimens and blood samples

This trial is a translational proof-of-concept, open-label, prospective cohort study of 60 patients aiming to identify the clinical markers and/or biomarkers associated with therapeutic response to immune checkpoints inhibitors, in patients with advanced melanoma.

The study will be conducted on a population of patients treated with ICI in the context of routine care, separated in two subgroups:

* Subgroup 1: patients treated with anti-PD-1 alone (nivolumab or pembrolizumab)
* Subgroup 2: patients treated with the combined treatment anti-PD-1+anti-CTLA-4 (nivolumab + ipilimumab)

For each included patient, blood samples will be collected during baseline visit and during treatment period (at Week 6 Day 1 and Week 12 Day 1).

If feasible, tumor biopsy (of primary tumor or metastasis) will be performed during baseline and on Week 12 Day 1 visit (predose). If tumor biopsy is not feasible, available archived tumor specimen (frozen or FFPE block) may be collected for the study.

All included patients will be followed-up for tumor status and/or survival status every 3 months until a maximum duration of 1 year from the first study dose.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Status of Immune Checkpoints at Gastrointestinal Cancer	NCT04566848	Gastrointestina...	Flow cytometric...	18 Years - 85 Years	Istanbul Training and Research Hospital
Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer	NCT05457075	Rectal Cancer	Immune checkpoi...	18 Years - 90 Years	Istanbul Training and Research Hospital
Evaluation of Sphingolipids as Predictive Biomarkers of Immune Checkpoint Inhibitor Response in Melanoma Patients	NCT03627026	Melanoma	Blood samples w...	18 Years -	Institut Claudius Regaud
Immune Checkpoints in Intraabdominal Ascites Fluid	NCT04540159	Colorectal Canc...	Flow-cytometric...	18 Years - 80 Years	Istanbul Training and Research Hospital
Evaluation of Sphingolipids as Predictive Biomarkers of Immune Checkpoint Inhibitor Response in Melanoma Patients	NCT03627026	Melanoma	Blood samples w...	18 Years -	Institut Claudius Regaud
Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer	NCT05457075	Rectal Cancer	Immune checkpoi...	18 Years - 90 Years	Istanbul Training and Research Hospital
Evaluation of the Role of Immune Checkpoints in Response to Breast Cancer Neoadjuvant Therapy	NCT05519397	Breast Cancer	Immune checkpoi...	18 Years - 88 Years	Istanbul Training and Research Hospital
TNF in Melanoma Patients Treated With Immunotherapy	NCT03348891	Melanoma	Tumor biopsy sp...	18 Years -	Institut Claudius Regaud

Spots Global Cancer Trial Database for immune checkpoints