Using of Costimulatory and co Inhibatory Immune Checkpoints as Diagnostic and Prognostic in Breast Cancer

Role of Soluble Immune Checkpoints Molecules as Diagnostic and Prognostic Markers in Breast Cancer Patients

Checkpoint proteins regulate the immune system; breast cancer cells exploit the up-regulation or down-regulation of these proteins to evade anti-tumour immune responses . It is now well recognized that advanced metastatic BC and early disease are associated with both localized and systemic immune dysfunction .in this study levels of soluble immune checkpoint molecules sTIM3 and sCD40 will be measured and compared with tissue form ,then follow up to patients' prognosis and the relation to markers levels.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer

Detailed Description

Breast cancer is the most common malignant tumour and the leading cause of cancer-associated mortality among women .Although comprehensive therapies exist, patient response to the treatments significantly varies, which partly attributed to varying antitumor immune responses .Immunotherapy is being recognized as a key therapeutic modality for cancer and represents one of the most promising therapies. Checkpoint proteins regulate the immune system. Breast cancer (BC) cells exploit the up-regulation or down-regulation of these proteins to evade anti-tumour immune responses. Notwithstanding the existence of profound immune dysregulation in advanced metastatic breast cancer (BC), it is now well recognized that early disease is also associated with both localized and systemic immune dysfunction . Recently, soluble co-inhibitory immune checkpoint molecules (ICMs) have been implicated as being potential mediators of the systemic immune dysregulation . Prominent among these soluble co inhibitory ICMs are: cytotoxic T-lymphocyte-associated protein (CTLA-4), programmed cell death protein 1 (PD-1) and its ligand, PD-L1, lymphocyte activation gene 3 (LAG-3) and T- Cell immunoglobulin and mucin-domain-containing protein 3 (TIM-3) . A study showed that resistance to anti-CTLA-4 or anti PD-1/PD-L1 inhibitors is compensated by up regulation of other immune checkpoints, such as Tim-3 . Consequently, Tim-3 has gained prominence as a potential candidate for cancer immunotherapy. Blocking Tim-3 with other checkpoint inhibitors has been shown to enhance antitumor immunity and suppress tumour growth in several preclinical tumour models. Increasing numbers of novel receptors and ligands have recently been found in the immune system. Some take part in a costimulatory interactions, such as Glucocorticoid-induced TNFR-related protein (GITR), GITR Ligand, CD27, CD28, CD40, CD80, CD86 and Inducible Co-Stimulator (ICOS) . CD40-CD40 ligand (CD40L) pathway is a member of the TNF superfamily and is expressed at various levels on antigen-presenting cells, epithelial cells, and hematopoietic progenitor cells . The CD40-CD40L costimulatory pathway has been shown to play a crucial role in humoral responses in humans, these cytokines modulate the function of T lymphocytes in antitumor responses. Few Review studies have reported the levels of sTIM-3 and CD40 in the literature, we are going to assess them and compare different stages of breast cancer .Previous study reported that, the level of Plasma concentration of the co-stimulatory immune checkpoint CD40 as well as the co-inhibitory molecule TIM-3 were all significantly lower in early breast cancer patients compared to healthy controls. Following neoadjuvant chemotherapy NAC, the plasma concentrations of the soluble co-stimulatory ICM sCD40 and soluble co inhibitory ICM sTIM-3 were significantly increased

• Study Type: Observational
• Enrollment (Estimated): 84

Contacts and Locations

• Study Contact: Name: Asmaa Mohammed, demostrator; Phone Number: 01140266310; Email: asmamohammed10101995@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Female patients with breast cancer and healthy females as controls

Description

Inclusion Criteria:

• Female patients with breast cancer aged > 18 years attending the Medical Oncology department of South Egypt Cancer Institute

Exclusion Criteria:

• Patients on chemotherapy
• A history of any other malignancy
• known (HIV) and/or hepatitis B or hepatitis C viruses,
• pregnancy or breast feeding
• patients or controls that refuse to be a part of the study.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
evaluate the levels of sTIM-3 and sCD40 in breast cancer patients in different stages and follow up their role in disease prognosis compared with healthy controls. Results will be compared with the previous studies.	study will take about 12months to be completed

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Lamiaa Fadel, lecturer, Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: December 5, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer and sCD40 and sTIM-3
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: Immune checkpoints in cancer

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No