Abstract: 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.
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Overview
This research article reviews the use of Bacillus Calmette-Guérin (BCG) immunotherapy for treating equine sarcoids, a common skin tumor in horses related to bovine papillomavirus infection.
It evaluates the immunological mechanisms behind BCG, clinical effectiveness, challenges, and compares it with other modern treatments, while suggesting future research directions.
Background and Context
Equine Sarcoids: The most frequent skin tumor in horses worldwide, often caused by bovine papillomavirus (BPV).
Clinical Challenge: Sarcoids have high recurrence rates after conventional treatments such as surgery, cryotherapy, or chemical agents.
BCG Immunotherapy: Historically used in veterinary oncology to stimulate the immune system in an attempt to regress or eliminate sarcoids.
Relevance: Despite its historical use, BCG’s role today is debated due to variable efficacy and potential side effects.
Methodology
The article is a narrative review based on a systematic literature search using PRISMA criteria.
A total of 55 studies from the last 40 years were evaluated.
Focus was on immunological mechanisms, clinical outcomes, therapy protocols, adverse effects, and comparative oncology perspectives.
Immunological Mechanisms of BCG in Sarcoid Treatment
Immune Activation: BCG stimulates both innate and adaptive immune responses.
Pattern Recognition: Through Toll-like receptors (TLR2 and TLR4), BCG activates macrophages and dendritic cells.
Cell Polarization: Macrophage polarization enhances inflammatory and cytotoxic responses against tumor cells.
Adaptive Responses: CD8+ T-cell activity is increased, promoting targeted killing of BPV-infected tumor cells.
Result: These mechanisms contribute to partial or complete regression of sarcoids in some cases.
Clinical Efficacy and Variability
BCG treatment results are highly variable across different cases.
Variability is linked to:
Differences in treatment protocols such as BCG dose, strain variation, and use of adjuvants.
Inconsistent induction of immune responses between individual horses.
Frequent adverse inflammatory reactions that can limit treatment tolerance.
Although some horses show sarcoid regression, these outcomes are not reliably reproducible.
Comparative Oncology and Alternative Therapies
Modern alternatives often demonstrate better outcomes and fewer side effects, including:
Cryotherapy: Freezing tumors with liquid nitrogen.
Carvalho M.C.P, Almeida G.B, Vieira R.R, Oliveira A.F, Silva F.L. Imunomodulação com vacina BCG para tratamento de sarcoide em um equino. Proceedings of the XI Simpósio Internacional do Cavalo Atleta; Belo Horizonte, MG, Brazil. 11–13 May 2023.
Page M.J, McKenzie J.E, Bossuyt P.M, Boutron I, Hoffmann T, Mulrow C.D, Shamseer L, Tetzlaff J.M, Akl E, Brennan S.E. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ 2021;372:n71.
Lidagoster S, Ben-David R, De Leon B, Sfakianos JP. BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer. Curr. Oncol. 2024;31:1063–1078.
Pereira M, Paixão E, Trajman A, de Souza RA, da Natividade MS, Pescarini JM, Pereira SM, Barreto FR, Ximenes R, Dalcomo M. The Need for Fast-Track, High-Quality and Low-Cost Studies about the Role of the BCG Vaccine in the Fight against COVID-19. Respir. Res. 2020;21:178.
Hannouneh ZA, Hijazi A, Alsaleem AA, Hami S, Kheyrbek N, Tanous F, Khaddour K, Abbas A, Alshehabi Z. Novel immuno-therapeutic options for BCG-unresponsive high-risk non-muscle-invasive bladder cancer. Cancer Med. 2023;12:21944–21968.
Youssef E, Palmer D, Fletcher B, Vaughn R. Exosomes in Precision Oncology and Beyond: From Bench to Bedside in Diagnostics and Therapeutics. Cancers 2025;17:940.
Kader M, Smith AP, Guiducci C, Wonderlich ER, Normolle D, Watkins SC, Barrat FJ, Barratt-Boyes SM. Blocking TLR7- and TLR9-Mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection. PLoS Pathog. 2013;9:e1003530.
Pandya A, Shah Y, Kothari N, Postwala H, Shah A, Parekh P, Chorawala MR. The Future of Cancer Immunotherapy: DNA Vaccines Leading the Way. Med. Oncol. 2023;40:200.
Verkuijl C, Smit J, Green JMH, Nordquist RE, Sebo J, Hayek MN, Hötzel MJ. Climate change, public health, and animal welfare: Towards a One Health approach to reducing animal agriculture’s climate footprint. Front. Anim. Sci. 2024;5:1281450.
Feng X, Li Z, Liu Y, Chen D, Zhou Z. CRISPR/Cas9 technology for advancements in cancer immunotherapy: From uncovering regulatory mechanisms to therapeutic applications. Exp. Hematol. Oncol. 2024;13:102.
Coman MA, Marcu A, Chereches RM, Leppälä J, Van Den Broucke S. Educational Interventions to Improve Safety and Health Literacy Among Agricultural Workers: A Systematic Review. Int. J. Environ. Res. Public Health 2020;17:1114.
Chehelgerdi M, Chehelgerdi M, Allela OQB, Pecho RDC, Jayasankar N, Rao DP, Thamaraikani T, Vasanthan M, Viktor P, Lakshmaiya N. Progressing nanotechnology to improve targeted cancer treatment: Overcoming hurdles in its clinical implementation. Mol. Cancer 2023;22:169.
Lorga AD, Amaro F, Gomes ARC, Cocco M, Gularte A, Silva Y, Silva J. Application of Euphorbia tirucalli Sap in Sarcoid Treatment in Horses—Case Report. Arq. Bras. Med. Vet. Zootec. 2022;74:509–513.
Brum JS, Souza TM, Barros CSL. Aspectos epidemiológicos e distribuição anatômica das diferentes formas clínicas do sarcoide equino no Rio Grande do Sul: 40 casos. Pesqui. Vet. Bras. 2010;30:839–843.
McConaghy FF, Davis RE, Reppas GP, Rawlinson RJ, McClintock SA, Hutchins DR, Hodgson DR. Management of equine sarcoids: 1975–1993. N. Z. Vet. J. 1994;42:180–184.
Walker M, Adams W, Hoskinson J, Held JP, Blackford J, Geiser D, Henton J. Iridium-192 brachytherapy for equine sarcoid, one and two year remission rates. Vet. Radiol. 1991;32:206–208.
Perez-Penco M, Byrdal M, Lara de la Torre L, Ballester M, Khan S, Siersbæk M, Lecoq I, Madsen CO, Kjeldsen JW, Svane IM. The Antitumor Activity of TGFβ-Specific T Cells Is Dependent on IL-6 Signaling. Cell Mol. Immunol. 2025;22:111–126.
Ahmed MM, Okesanya OJ, Othman ZK, Ibrahim AM, Adigun OA, Ukoaka BM, Abdi MI, Lucero-Prisno DE. Holistic Approaches to Zoonoses: Integrating Public Health, Policy, and One Health in a Dynamic Global Context. Zoonotic Dis. 2025;5:5.
Singh S, Saavedra-Avila NA, Tiwari S, Porcelli SA. A Century of BCG Vaccination: Immune Mechanisms, Animal Models, Non-Traditional Routes and Implications for COVID-19. Front. Immunol. 2022;13:959656.