Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
93 participants
OBSERVATIONAL
2022-07-01
2024-05-31
Brief Summary
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CD155 expression was associated with an unfavorable prognosis in solid tumors such as colon cancer, breast cancer, lung adenocarcinoma, pancreatic cancer, melanoma, and glioblastoma, as it correlated with tumor migration, development of metastases, tissue and lymph node invasion, relapse, and poorer survival.
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Detailed Description
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T-cell exhaustion is a state of decline in T-cell proliferation and function (secretion of cytokines and cytotoxicity). It is defined by the expression of immune checkpoints including programmed cell death protein-1 (PD1), cytotoxic T-lymphocyte-associated protein-4 (CTLA4), T-cell immunoglobulin and mucin-domain containing-3 (TIM3), lymphocyte-activation gene-3 (LAG3), T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT), and CD160. This phenomenon was observed in many cancer cells to escape from antitumor immune responses.
The poliovirus receptor (PVR), also known as CD155, is an immunoglobulin -like adhesion molecule, with an important regulatory role in T-cell and natural killer (NK) cell functions, cell migration and proliferation. It is a major ligand that is expressed on epithelial and myeloid cells of the tumor. PVR is able to bind CD226, DNAX accessory molecule-1 (DNAM-1), T-cell-Activated Increased Late Expression Protein (TACTILE), and TIGIT. Binding to DNAM-1 induces the release of pro-inflammatory cytokines and cytotoxicity of T-cells and NK cells (T-cell activation), while binding to TIGIT induces a rather anti-inflammatory, non-proliferative, and noncytotoxic profile (T-cell exhaustion).
CD155 expression was associated with an unfavorable prognosis in solid tumors such as colon cancer, breast cancer, lung adenocarcinoma, pancreatic cancer, melanoma, and glioblastoma, as it correlated with tumor migration, development of metastases, tissue and lymph node invasion, relapse, and poorer survival.
Stamm et al., demonstrated that high CD155 (PVR) expression correlated with poor outcome in AML. Stamm et al., also showed that antibody blockade of PVR on AML cell lines or primary AML cells or TIGIT blockade on immune cells increased the anti-leukemic effects mediated by purified CD3+ cells in vitro. Zhang et al., assessed the prognostic significance and immune-associated mechanism of CD155 and identified that CD155 was commonly upregulated in most human cancers including AML, and high expression of CD155 was closely correlated with unfavorable clinical outcomes.
Our aim is to study the prognostic and predictive values of CD155 expression in AML patients in our locality.
Conditions
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Study Design
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CASE_ONLY
CROSS_SECTIONAL
Study Groups
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AML Patients
Adult patients (from 18 - 60 years) diagnosed as AML
Flow cytometric immunophenotyping
CD155 expression by flow cytometric immunophenotyping
Complete blood count
Complete blood count with peripheral blood smear examination
Bone marrow aspiration
Bone marrow aspiration at both diagnosis and follow up of patients
Cytogenetic testing
Karyotyping or AML fluorescence in situ hybridization (FISH) panel for diagnosis and risk stratification of AML patients
FLT3-ITD using High resolution melting curve (HRM) analysis
Detection of FLT3-ITD mutation in AML patinets
Interventions
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Flow cytometric immunophenotyping
CD155 expression by flow cytometric immunophenotyping
Complete blood count
Complete blood count with peripheral blood smear examination
Bone marrow aspiration
Bone marrow aspiration at both diagnosis and follow up of patients
Cytogenetic testing
Karyotyping or AML fluorescence in situ hybridization (FISH) panel for diagnosis and risk stratification of AML patients
FLT3-ITD using High resolution melting curve (HRM) analysis
Detection of FLT3-ITD mutation in AML patinets
Eligibility Criteria
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Inclusion Criteria
* Age group: patients more than 18 years old and less than 60 years.
* Patients receiving induction chemotherapy 3\&7 at South Egypt Cancer Institute.
Exclusion Criteria
* Patients with concurrent malignancy.
* Secondary AML.
* Acute Promyelocytic leukemia (AML-M3).
18 Years
60 Years
ALL
No
Sponsors
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Assiut University
OTHER
Responsible Party
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Nehal Adel Rayan Mohamed
Assistant Lecturer
Principal Investigators
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Nehal Rayan, M.D.
Role: PRINCIPAL_INVESTIGATOR
Assistant Lecturer
Locations
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South Egypt Cancer Institute, Assiut University
Asyut, , Egypt
Countries
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References
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Dougall WC, Kurtulus S, Smyth MJ, Anderson AC. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol Rev. 2017 Mar;276(1):112-120. doi: 10.1111/imr.12518.
Gao J, Zheng Q, Xin N, Wang W, Zhao C. CD155, an onco-immunologic molecule in human tumors. Cancer Sci. 2017 Oct;108(10):1934-1938. doi: 10.1111/cas.13324. Epub 2017 Aug 18.
Gorvel L, Olive D. Targeting the "PVR-TIGIT axis" with immune checkpoint therapies. F1000Res. 2020 May 13;9:F1000 Faculty Rev-354. doi: 10.12688/f1000research.22877.1. eCollection 2020.
Li XY, Das I, Lepletier A, Addala V, Bald T, Stannard K, Barkauskas D, Liu J, Aguilera AR, Takeda K, Braun M, Nakamura K, Jacquelin S, Lane SW, Teng MW, Dougall WC, Smyth MJ. CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms. J Clin Invest. 2018 Jun 1;128(6):2613-2625. doi: 10.1172/JCI98769. Epub 2018 May 14.
Liu L, Chang YJ, Xu LP, Zhang XH, Wang Y, Liu KY, Huang XJ. T cell exhaustion characterized by compromised MHC class I and II restricted cytotoxic activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Clin Immunol. 2018 May;190:32-40. doi: 10.1016/j.clim.2018.02.009. Epub 2018 Mar 15.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30. doi: 10.3322/caac.21590. Epub 2020 Jan 8.
Zhang H, Yang Z, Du G, Cao L, Tan B. CD155-Prognostic and Immunotherapeutic Implications Based on Multiple Analyses of Databases Across 33 Human Cancers. Technol Cancer Res Treat. 2021 Jan-Dec;20:1533033820980088. doi: 10.1177/1533033820980088.
Bakhshaei P, Kazemi MH, Golara M, Abdolmaleki S, Khosravi-Eghbal R, Khoshnoodi J, Judaki MA, Salimi V, Douraghi M, Jeddi-Tehrani M, Shokri F. Investigation of the Cellular Immune Response to Recombinant Fragments of Filamentous Hemagglutinin and Pertactin of Bordetella pertussis in BALB/c Mice. J Interferon Cytokine Res. 2018 Apr;38(4):161-170. doi: 10.1089/jir.2017.0060.
Other Identifiers
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SECI-IRB-IORG0006563-545
Identifier Type: OTHER
Identifier Source: secondary_id
SECI-CD155
Identifier Type: -
Identifier Source: org_study_id
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