BTLA: An Emerging Immune Checkpoint Target in Cancer Immunotherapy.
Journal
Pharmaceuticals (Basel, Switzerland)
Journal Volume
18
Journal Issue
12
Start Page
Article number 1784
ISSN
1424-8247
Date Issued
2025-11-24
Author(s)
Abstract
B and T lymphocyte attenuator (BTLA) is a unique co-inhibitory receptor of the CD28 immunoglobulin superfamily that exhibits dual regulatory functions in immune activation and tolerance. Unlike PD-1 or CTLA-4, BTLA interacts bidirectionally with its ligand HVEM, forming a complex signaling network that shapes immune homeostasis within the tumor microenvironment. Dysregulated BTLA expression has been associated with tumor immune evasion and poor prognosis in several cancers. Owing to its distinctive molecular features and multifaceted immunoregulatory roles, BTLA represents an emerging therapeutic target, particularly in tumors unresponsive to conventional immune checkpoint inhibitors. This review provides a comprehensive overview of BTLA's structure, signaling mechanisms, and functional implications in tumor immunity and discusses current advances and challenges in BTLA-targeted therapy. Finally, we outline future perspectives on leveraging BTLA modulation to enhance cancer immunotherapy outcomes.
Subjects
B and T lymphocyte attenuator
BTLA
cancer immunotherapy
clinical applications
immune checkpoint
oncology
Type
review article