Peer-reviewed veterinary case report
High blood PD-L2 levels found in cats with mammary cancer
By João, Vitória Silva et al.·Published in Scientific reports·2026·Faculty of Veterinary Medicine·View original on PubMed →
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Original publication title: Serum programmed death ligand 2 is elevated in cats with mammary carcinoma.
- Species:
- cat
Plain-English summary
A cat with mammary cancer was found to have high levels of a protein called PD-L2 in its blood, which could help diagnose and understand the disease better. Researchers discovered that cats with certain aggressive types of mammary cancer, like HER2-positive and Triple-Negative, had even higher levels of this protein. The study suggests that measuring PD-L2 could be useful for veterinarians in identifying the severity of the cancer and potentially guiding treatment options in the future. This finding may lead to better management strategies for cats suffering from mammary carcinoma.
People also search for: cat mammary cancer symptoms · elevated PD-L2 in cats · HER2-positive cat cancer treatment
Abstract
Since the PD-1/PD-L1/PD-L2 axis plays a vital role in immune tolerance and T-cell exhaustion, having emerged as a target for breast cancer immunotherapy, we investigated the relevance of serum PD-L2 (sPD-L2) levels in feline mammary carcinoma (FMC), to validate its potential use as a diagnostic and/or prognostic biomarker, and as a future target for immunotherapy. To accomplish that, sPD-L2 levels were quantified by enzyme-linked immunosorbent assay and compared between healthy control cats and cats with mammary carcinoma, also stratified by tumor molecular subtype. Statistical associations between sPD-L2 levels, clinicopathological features and other serum immune checkpoint molecules (sPD-1, sPD-L1, sCTLA-4, sTNF-α, sVEGF-A, sVEGFR-1, sVEGFR-2 and sLAG-3) were also analyzed. Results revealed that sPD-L2 levels were significantly higher in the FMC group (p < 0.0001), with a concentration of 1934 pg/mL established as the best cut-off value to distinguish sick from healthy cats (specificity: 96.6%; sensitivity: 93.6%; AUC = 0.980). Interestingly, cats with HER2-positive or Triple-Negative (TN) mammary carcinoma subtypes showed higher sPD-L2 levels (p < 0.0001). According to receiver-operating characteristic (ROC) curve analysis, a serum PD-L2 concentration of 5499 pg/mL represented the optimal cut-off for distinguishing cats with these two subtypes from cats with Luminal A (LA) and Luminal B (LB) carcinomas (specificity: 95.2%; sensitivity: 82.6%; AUC = 0.919). Furthermore, in the FMC group, positive correlations were found between sPD-L2 levels and sCTLA-4 (r = 0.496, p = 0.001), sTNF-α (r = 0.482, p = 0.0009), sVEGF-A (r = 0.54, p = 0.0002), sVEGFR-1 (r = 0.339, p = 0.025), sVEGFR-2 (r = 0.322, p = 0.033) and sLAG-3 levels (r = 0.324, p = 0.032). Finally, significant associations were found between sPD-L2 levels and progesterone receptor (PR) status (p = 0.002), HER2 status (p = 0.009) and Ki-67 index (p < 0.0001). A serum sPD-L2 concentration of 3732 pg/mL was identified as the optimal cut-off value for distinguishing FMCs with a high Ki-67 index (≥ 14%) from those with a low index (specificity: 80.0%; sensitivity: 94.1%; AUC = 0.906). In conclusion, our findings suggest that sPD-L2 is a potential biomarker for FMC, particularly in HER2-positive and TN subtypes.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/41735450/