Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT06169007 |
Other study ID # |
Immune checkpoints in cancer |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
May 1, 2024 |
Est. completion date |
December 1, 2025 |
Study information
Verified date |
December 2023 |
Source |
Assiut University |
Contact |
Asmaa Mohammed, demostrator |
Phone |
01140266310 |
Email |
asmamohammed10101995[@]aun.edu.eg |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
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.
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