Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer
Condition: Rectal Cancer
MeSH terms: Rectal Neoplasms
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Immune checkpoint measure
Intervention type(s): Diagnostic Test
Intervention description(s): The measurement of soluble immune checkpoints of stage II-III rectal cancer before neoadjuvant treatment
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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
      
Biospecimen description: 
      Plasma of the rectal cancer patients
    
Keywords: Neoadjuvant Therapy; Rectal Cancer; Immune Checkpoints