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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

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT05457075
Enrollment
38
Registered
2022-07-13
Start date
2022-05-01
Completion date
2023-02-15
Last updated
2023-05-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rectal Cancer

Keywords

Neoadjuvant Therapy, Rectal Cancer, Immune Checkpoints

Brief 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.

Interventions

DIAGNOSTIC_TESTImmune checkpoint measure

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

Sponsors

Istanbul Training and Research Hospital
Lead SponsorOTHER_GOV

Study design

Observational model
CASE_ONLY
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No

Inclusion criteria

* Over 18 years old, * Patients who will receive neoadjuvant therapy with clinically and histopathologically proven stage II-III rectal cancer

Exclusion criteria

* Known immunodeficiency * Having a primary malignancy other than rectal cancer, * Pregnants, * Patients younger than 18 years and older than 90 years, * Patients who refused to participate in the study

Design outcomes

Primary

MeasureTime frameDescription
Soluble immune checkpointsBefore neoadjuvant treatmentsCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9

Countries

Turkey (Türkiye)

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026