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Association between ultraviolet-related TP53 mutations and immune microenvironment in equine ocular squamous cell carcinoma.
Abstract: This study investigates the molecular and immune characteristics of equine ocular squamous cell carcinoma (eoSCC). Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to detect protein expression and TP53 mutations, respectively. T lymphocytes (CD3+), regulatory T cells (FoxP3+), B lymphocytes (CD20+), and macrophages (IBA-1+) were quantified. A total of 29 cases of eoSCC were evaluated, consisting of 3/29 carcinomas in situ (CISs) and 26/29 squamous cell carcinomas (SCCs). p53 positivity by IHC was detected in 19/29 cases while by NGS, 21 TP53 mutations were found in 13/29 cases (44.83%), of which 18/21 were C > T base substitutions, typical of ultraviolet (UV)-induced DNA damage. In tumors with TP53 mutations, IBA-1⁺ macrophages were significantly increased (p = 0.001) and CD3⁺ T lymphocytes were also more abundant (p = 0.028) than in wild type TP53 cases, whereas CD20⁺ B lymphocytes and FoxP3⁺ regulatory T lymphocytes showed no significant differences. Equus caballus papillomavirus type 2 positivity was detected in 6/29 cases (20.69%) via in situ hybridization (ISH), but viral presence did not impact immune cell infiltration. Ki67 scores were higher in SCCs/CISs withTP53 mutations, but the difference was not statistically significant. Overall, TP53 mutations appear to contribute to eoSCC development, potentially as a consequence of UV-light exposure, and to influence immune cell infiltration.
Publication Date: 2026-02-26 PubMed ID: 41748902PubMed Central: PMC13046799DOI: 10.1038/s41598-026-41467-6Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
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Overview
- This study examines ultraviolet (UV)-related mutations in the TP53 gene and how these mutations affect the immune microenvironment in equine ocular squamous cell carcinoma (eoSCC), a type of eye cancer in horses.
- The researchers analyzed tumor samples for TP53 mutations, immune cell types, and viral presence to understand the relationship between genetic changes and immune response within the tumors.
Background and Purpose
- Equine ocular squamous cell carcinoma (eoSCC) is a common eye tumor in horses, linked to UV exposure and possibly viral infection.
- The TP53 gene is a tumor suppressor frequently mutated in cancers; UV light typically causes specific mutations characterized by C > T base substitutions.
- The immune microenvironment, including various immune cells such as T lymphocytes, B lymphocytes, regulatory T cells, and macrophages, plays a critical role in cancer progression and response to therapy.
- This study aimed to investigate the presence of TP53 mutations in eoSCC, their UV-related nature, and any associations with the tumor immune microenvironment and viral infection.
Methods
- Sample Population: 29 tumor cases from horses, including 3 carcinomas in situ (CIS) and 26 invasive squamous cell carcinomas (SCCs).
- Protein Expression: Immunohistochemistry (IHC) was used to detect p53 protein expression and quantify immune cells:
- CD3+ T lymphocytes
- FoxP3+ regulatory T cells
- CD20+ B lymphocytes
- IBA-1+ macrophages
- Mutation Analysis: Next-generation sequencing (NGS) was applied to identify TP53 mutations in tumor DNA.
- Viral Detection: In situ hybridization (ISH) assessed the presence of Equus caballus papillomavirus type 2 (EcPV2).
- Proliferation Marker: Ki67 scores were evaluated to assess tumor cell proliferation.
Key Findings
- TP53 Mutations:
- TP53 mutations were found in 13 out of 29 cases (44.83%).
- Most mutations (18 out of 21) were C > T substitutions, typical of UV-induced DNA damage.
- p53 protein was expressed (positive by IHC) in 19/29 cases, indicating aberrant p53 accumulation often linked with mutations.
- Immune Cell Infiltration:
- TP53-mutated tumors had significantly higher numbers of IBA-1+ macrophages (p = 0.001) and CD3+ T lymphocytes (p = 0.028) compared to tumors with wild-type TP53.
- No significant differences were observed in CD20+ B lymphocytes or FoxP3+ regulatory T cells between mutated and wild-type TP53 tumors.
- Viral Infection:
- EcPV2 was detected in 6/29 cases (20.69%).
- Presence of the virus did not significantly affect immune cell infiltration.
- Tumor Proliferation:
- Ki67 scores, indicative of tumor cell proliferation, tended to be higher in TP53-mutated tumors but the difference was not statistically significant.
Interpretation and Implications
- The predominance of C > T mutations in TP53 suggests that UV exposure is a major factor driving eoSCC development in horses.
- These UV-induced TP53 mutations are associated with increased infiltration of immune cells, especially macrophages and T lymphocytes, which may reflect an immune response to tumor cells harboring genetic mutations.
- The increased presence of immune cells in mutated tumors points to an interaction between genetic damage and the immune microenvironment that could influence tumor progression and response to treatment.
- EcPV2 infection appears to have a limited role in modulating immune responses in these tumors.
- Understanding these molecular and immune characteristics may guide future therapeutic strategies targeting the immune system or preventing UV-related genetic damage in horses.
Summary
- This study provides evidence that UV-related TP53 mutations contribute to the pathogenesis of equine ocular squamous cell carcinoma and influence the tumor’s immune environment.
- These findings enhance knowledge about the mechanisms of tumor development and immune interactions in veterinary oncology and may have parallels in human UV-associated cancers.
Cite This Article
APA
Martinoli G, De Biase D, Ressel L, Brunetti B, Avallone G, Grillini A, Franceschini T, Fiorentino M, Sarli G, Bacci B.
(2026).
Association between ultraviolet-related TP53 mutations and immune microenvironment in equine ocular squamous cell carcinoma.
Sci Rep, 16(1), 11151.
https://doi.org/10.1038/s41598-026-41467-6 Publication
Researcher Affiliations
- Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, Ozzano dell'Emilia, 40064, Bologna, BO, Italy.
- Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, Bologna, Italy.
- Department of Veterinary Anatomy Physiology and Pathology, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health & Life Sciences, University of Liverpool, Liverpool, CH64 7TE, UK.
- Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, Ozzano dell'Emilia, 40064, Bologna, BO, Italy.
- Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, Ozzano dell'Emilia, 40064, Bologna, BO, Italy.
- Pathology Unit, Dipartimento Interaziendale di Anatomia Patologica di Bologna (DIAP), Maggiore Hospital, Bologna, Italy.
- Pathology Unit, Dipartimento Interaziendale di Anatomia Patologica di Bologna (DIAP), Maggiore Hospital, Bologna, Italy.
- Pathology Unit, Dipartimento Interaziendale di Anatomia Patologica di Bologna (DIAP), Maggiore Hospital, Bologna, Italy.
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
- Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, Ozzano dell'Emilia, 40064, Bologna, BO, Italy.
- Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Via Tolara di Sopra 50, Ozzano dell'Emilia, 40064, Bologna, BO, Italy. barbara.bacci@unibo.it.
MeSH Terms
- Animals
- Carcinoma, Squamous Cell / genetics
- Carcinoma, Squamous Cell / veterinary
- Carcinoma, Squamous Cell / immunology
- Carcinoma, Squamous Cell / pathology
- Horses
- Tumor Suppressor Protein p53 / genetics
- Tumor Suppressor Protein p53 / metabolism
- Mutation
- Tumor Microenvironment / immunology
- Tumor Microenvironment / genetics
- Tumor Microenvironment / radiation effects
- Eye Neoplasms / genetics
- Eye Neoplasms / veterinary
- Eye Neoplasms / immunology
- Eye Neoplasms / pathology
- Ultraviolet Rays / adverse effects
- Horse Diseases / genetics
- Horse Diseases / immunology
- Horse Diseases / pathology
- B-Lymphocytes / immunology
- Macrophages / immunology
- T-Lymphocytes, Regulatory / immunology
Conflict of Interest Statement
Declarations. Competing interests: The authors declare no competing interests.
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