Expression of CD274 (PD-L1) and CD276 in B-cell Malignancies: A Study by Flowcytometry

Official title

Expression of CD274 (PD-L1) and CD276 in B-cell Malignancies: A Study by Flowcyometry

Overview

B-cell malignancies include a spectrum of cancers originating from abnormal B lymphocytes at different developmental stages (1) that affect the peripheral blood (PB), bone marrow (BM), and lymphatic system. They can be categorized into leukemias and lymphomas. Each has unique characteristics, depending on the type of cells affected, and different behaviors, ranging from chronic conditions with slow progression to aggressive forms that require immediate treatment (2). Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in childhood and the predominant form of precursor B-cell leukemia globally, accounting for 85% of ALL cases. According to recent global burden estimates, ALL incidence increased to over 100 000 cases worldwide by 2021, corresponding to an age-standardized incidence rate of \~1.4 per 100 000 persons per year (3). Its quick course and possibility of systemic involvement make early and prompt diagnosis and efficient treatment essential for enhancing long-term survival, especially in young patients.(4). B-Chronic lymphoproliferative disorders (B-CLPDs) are a diverse collection of illnesses that are defined by the uncontrolled and clonal expansion of mature B cells. Although they can range from indolent to aggressive, they usually impact elderly persons and have a slow-growing, indolent clinical history. These conditions account for more than 90% of all chronic lymphoid cancers (5). B-cell malignancies arise from disruption of immune system regulation through alterations in crucial signaling pathways, such as the B-cell receptor (BCR) signalling defect, imbalance between stimulatory signals (that drive proliferation and differentiation) and inhibitory signals (that enforce tolerance and prevent overstimulation) leading to anti-tumor immunity with development and metastasis of cancer cells (6). An essential part of the immune regulatory system for malignancies, the B7-H family which is an important immune checkpoint provides new opportunities for modifying the tumor microenvironment (TME). This family is well-known for its several functions in controlling both innate and adaptive immunity. It is also involved in the recruitment and polarization of diverse immune cells and can have co-stimulatory or co-inhibitory effects on T cells, affecting processes like T cell activation, differentiation, and effector functions. Two important members in this family are: B7-H1 (PD-L1) also known CD274 and B7-H3 (CD276) (7). Firstly, PD-L1 (CD274) which bind to PD-1 . This interaction primarily result in suppresses effector T cell activity while promoting the activity of immunosuppressive regulatory T cells (Tregs), hence negatively regulating the adaptive immune response. However, in malignancy, cancer cells promote the PD-1/PD-L1 axis to cause immune escape in cancer development and progression (8). It was reported that PD-L1 is widely expressed in solid tumors like melanoma and non-small cell lung cancer (9). Secondly, CD276, also called B7-H3, is abundantly expressed in cancer cells and activated tumor-infiltrating immune cells aiding in the evasion of cytotoxic T-cell and natural killer cell surveillance (10). According to new research, B7-H3 contributes to tumor growth, metastasis, and resistance to treatment, all of which have a negative impact on patient outcomes (11). Till now, the co-expression and functional relationship of CD274 and CD276 in B-cell malignancies remain poorly recognized. Understanding whether malignant B cells utilize multiple immune checkpoint pathways simultaneously may explain resistance to immunotherapy and identify novel prognostic and therapeutic targets.

Primary outcome measures

• Using CD274 and CD276 in diagnosis of B-cell malignancies using Flowcytometric technique [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

Newly diagnosed patients of both gender at any age with

• Acute B- lymphoblastic leukemia. or
• B- lymphoproliferative disorders (whether chronic lymphocytic leukemia or any other disorder)

Exclusion criteria

• Patients with any other type of malignancies.
• Patients that receiving chemotherapy.
• Patients with any autoimmune diseases

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Castellanos JR, Purvis IJ, Labak CM, Guda MR, Tsung AJ, Velpula KK, Asuthkar S. B7-H3 role in the immune landscape of cancer. Am J Clin Exp Immunol. 2017 Jun 15;6(4):66-75. eCollection 2017. PMID 28695059
• Flem-Karlsen K, Fodstad O, Tan M, Nunes-Xavier CE. B7-H3 in Cancer - Beyond Immune Regulation. Trends Cancer. 2018 Jun;4(6):401-404. doi: 10.1016/j.trecan.2018.03.010. Epub 2018 Apr 20. PMID 29860983
• Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Calio A, Cuppone F, Sperduti I, Giannarelli D, Chilosi M, Bronte V, Scarpa A, Bria E, Tortora G. Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers. PLoS One. 2015 Jun 18;10(6):e0130 PMID 26086854
• Lin X, Kang K, Chen P, Zeng Z, Li G, Xiong W, Yi M, Xiang B. Regulatory mechanisms of PD-1/PD-L1 in cancers. Mol Cancer. 2024 May 18;23(1):108. doi: 10.1186/s12943-024-02023-w. PMID 38762484
• Luo Y, Yuan Y, Liu D, Peng H, Shen L, Chen Y. Targeting novel immune checkpoints in the B7-H family: advancing cancer immunotherapy from bench to bedside. Trends Cancer. 2025 Jun;11(6):540-559. doi: 10.1016/j.trecan.2025.02.007. Epub 2025 Mar 19. PMID 40113530
• Sun H, Huang D, Zhang H, Dong M, Wang S, Sun M, et al. Targeting Immune Checkpoints: Basic Signaling Pathways and Clinical Translation in Cancer Therapeutics. MedComm - Oncology. 2025;4(3):e70030.
• Chen C, Gu YD, Geskin LJ. A Review of Primary Cutaneous CD30+ Lymphoproliferative Disorders. Hematol Oncol Clin North Am. 2019 Feb;33(1):121-134. doi: 10.1016/j.hoc.2018.08.003. PMID 30497669
• Fan H, Yang Y, Lu Y, Li J, Huang Z, Ren Z, Zhou B. Global burden of acute lymphoblastic leukemia following the COVID-19 pandemic. Ann Hematol. 2025 Sep;104(9):4713-4727. doi: 10.1007/s00277-025-06639-w. Epub 2025 Oct 11. PMID 41074983

Identifiers

NCT: NCT07515313 · dyuhufhjdfvhbffd

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗