PD-1, PD-L1, and PD-L2 Expression as Predictive Markers in Rare Feline Mammary Tumors

Maria Franco ^1,2, Fernanda Seixas ^2,3,4, Maria Dos Anjos Pires ^2,3,4

¹CIISA-Center of Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisboa, Portugal.
²Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisboa, Portugal.
³Veterinary Sciences Department, University of Trás-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal.
⁴Animal and Veterinary Research Centre (CECAV), UTAD, 5000-801 Vila Real, Portugal.
⁵ICBAS-UP, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal.
⁶Animal Science and Study Centre/Food and Agrarian Sciences and Technologies Institute (CECA/ICETA), 4050-478 Porto, Portugal.
⁷Centre for Investigation Vasco da Gama (CIVG), Department of Veterinary Sciences, Vasco da Gama University School, 3020-210 Coimbra, Portugal.
⁸Onevetgroup Hospital Veterinário do Baixo Vouga (HVBV), 3750-742 Águeda, Portugal.
⁹DNAtech Veterinary Laboratory, 1649-038 Lisboa, Portugal.
¹⁰Faculty of Veterinary Medicine, Universidade Lusófona de Humanidades e Tecnologias, 1749-024 Lisboa, Portugal.
¹¹Laboratório Associado para a Química Verde (LAQV), Rede de Química e Tecnologia (REQUIMTE), University of Porto, 4050-453 Porto, Portugal.

⁰CIISA-Center of Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisboa, Portugal.

Veterinary Sciences +

|

August 28, 2025

View abstract on PubMed

Summary

This study investigated the PD-1/PD-L1/PD-L2 immune checkpoint in feline mammary carcinoma (FMC). Findings suggest this pathway is relevant in rare FMC subtypes, potentially offering new immunotherapy targets.

Area Of Science

Veterinary Oncology
Immunology
Cancer Research

Background

Feline mammary carcinoma (FMC) is an aggressive cancer with limited treatment options.
The PD-1/PD-L1/PD-L2 axis is crucial in human breast cancer immunotherapy.
Understanding this axis in feline cancers is vital for developing new treatments.

Purpose Of The Study

To evaluate the expression of PD-1 and its ligands (PD-L1, PD-L2) in rare feline mammary carcinoma histotypes.
To correlate PD-1/PD-L1/PD-L2 expression with clinicopathological features of FMC.
To explore the potential of targeting the PD-1/PD-L1/PD-L2 pathway in FMC.

Main Methods

Immunohistochemistry (IHC) was used to assess PD-1, PD-L1, and PD-L2 expression.
Analysis included tumor cells (TCs), intratumoral lymphocytes (iTILs), and stromal tumor-infiltrating lymphocytes (sTILs).
Expression levels were correlated with biological behavior and clinical data.

Main Results

PD-1, PD-L1, and PD-L2 were expressed in various cell types within FMC tumors.
PD-1 expression in TCs correlated with less aggressive tumor behavior.
PD-L1 in iTILs was associated with skin ulceration, while PD-L2 in TCs was linked to its absence.

Conclusions

The PD-1/PD-L1/PD-L2 immune checkpoint is relevant in rare feline mammary carcinoma subtypes.
Expression patterns suggest a role in FMC pathogenesis and potential therapeutic implications.
Further research into checkpoint-blockade therapies for FMC is warranted.

Keywords:

PD-1/PD-L1/PD-L2 immunoregulatory axis biomarkers immunotherapy tumor expression