BCG Immunotherapy in Equine Sarcoid Treatment: Mechanisms, Clinical Efficacy, and Challenges in Veterinary Oncology.

Equine sarcoids are the most common dermatological neoplasm in horses worldwide, associated with bovine papillomavirus (BPV) infection and characterized by high recurrence rates after conventional therapies. Bacillus Calmette-Guérin (BCG) immunotherapy has historically been used for sarcoid treatment, yet its role in contemporary veterinary oncology remains debated. This narrative review critically examines the immunological mechanisms, clinical efficacy, and limitations of BCG in equine sarcoid therapy, while integrating insights from comparative oncology and One Health perspectives. A systematic search following PRISMA-based criteria identified 55 relevant studies published over the past four decades. Evidence indicates that BCG activates innate and adaptive immunity through TLR2/4 signaling, macrophage polarization, and enhanced CD8+ T-cell responses, leading to partial or complete sarcoid regression in select cases. However, therapeutic outcomes are highly variable due to heterogeneity in protocols (dose, strain, adjuvant use) and frequent adverse inflammatory reactions. Comparative analyses highlight that modern alternatives-such as cryotherapy, cisplatin-based protocols, and topical imiquimod-achieve higher efficacy and lower recurrence rates in many clinical settings. Although BCG is now rarely considered a first-line therapy, it remains relevant in resource-limited regions, such as the Amazon Biome, where cost-effectiveness and accessibility are critical. Future directions include randomized controlled trials, standardized protocols, and innovative approaches such as checkpoint inhibition, CRISPR-Cas9 targeting of viral oncogenes, and nanoparticle delivery systems. This review provides a balanced and data-driven synthesis of BCG immunotherapy, clarifying its historical contributions, current limitations, and translational opportunities for advancing equine and comparative oncology.