VISTA Is a Diagnostic Biomarker and Immunotherapy Target of Aggressive Feline Mammary Carcinoma Subtypes

Abstract

Feline mammary carcinoma (FMC) is a common neoplasia, showing aggressive clinicopathological features, without viable therapeutic options. The study of tumor microenvironment has gained importance, due to the ability to control tumor progression by regulating the immune response. Considering the lack of knowledge, feline serum VISTA levels from cats with mammary carcinoma were compared with healthy controls, and with serum levels of PD-1/PD-L1, CTLA-4, LAG-3, IL-6, and TNF-α. In parallel, VISTA tumor expression was evaluated in FMC samples. The obtained data revealed that serum VISTA levels were significantly higher in cats presenting HER2-positive (p = 0.0025) or triple-negative subtypes (p = 0.0019), with higher serum levels in luminal A (p = 0.0025) correlated to the presence of metastasis (p = 0.0471). Furthermore, in HER2-positive or triple-negative tumors, correlations were obtained between serum VISTA levels and the serum levels of the above-mentioned molecules. In tumors, VISTA expression revealed a stronger intensity in cancer cells, when compared to TILs (p < 0.0001). Stratifying the samples by subtypes, a higher number of VISTA-positive TILs was observed in the HER2-positive subtype, compared with triple-negative tumors (p = 0.0138). In conclusion, results support the development of therapeutic strategies for HER2-positive and triple-negative FMC subtypes, reinforcing the use of cats as a human oncology model.

Comparative Evaluation of Tumor-Infiltrating Lymphocytes in Companion Animals: Immuno-Oncology as a Relevant Translational Model for Cancer Therapy

“…However, this was not correlated with outcome. In this same study, the percentage of VISTA-positive TILs was also higher in grade II ( p = 0.0025) tumors when compared to grade I [ 108 ]. Cytokines that were associated with tumor growth and metastasis (IL-1 and IL-6) are upregulated, particularly in canine metastatic mammary carcinoma samples.…”

“…Total PD-1 and PD-L1 scoring of TILs and cancer cells are significantly elevated in HER2-positive mammary carcinomas in felines compared to the triple-negative normal-like subtype, similar to what is seen in human HER2-positive breast cancer [ 63 ]. V-domain immunoglobulin suppressor of T-cell activation (VISTA)-positive TILs have also been evaluated in feline mammary carcinoma, and by stratifying based on subtype, cats with HER2-positive disease had a significantly higher proportion of VISTA-positive TILs than those with the triple-negative subtype ( p = 0.0138) [ 108 ]. However, this was not correlated with outcome.…”

Arene–Arene Coupled Disulfamethazines (or Sulfadiazine)-Phenanthroline-Metal(II) Complexes were Synthesized by In Situ Reactions and Inhibited the Growth and Development of Triple-Negative Breast Cancer through the Synergistic Effect of Antiangiogenesis, Anti-Inflammation, Pro-Apoptosis, and Cuproptosis

“…10 Andreia Gameiro team found that cats with breast cancer had elevated levels of VEGF-A, VEGFR-1, and VEGFR-2, especially in more malignant breast cancer. 11 Nowadays, VEGF has become one of the hot spots in the research of antitumor drugs. Because in addition to its expression in endothelium cells, it is also excessively expressed among diverse cancer types, such as breast cancer, 12 soft tissue sarcoma, 13 gastric cancer, 14 rectal cancer, 15 and lung cancer.…”

“…Daniel J Schoeffner team found that VEGF-A could induce cancer cell proliferation in a mouse model of breast cancer . Andreia Gameiro team found that cats with breast cancer had elevated levels of VEGF-A, VEGFR-1, and VEGFR-2, especially in more malignant breast cancer . Nowadays, VEGF has become one of the hot spots in the research of antitumor drugs.…”

The Implication of Serum Autoantibodies in Prognosis of Canine Mammary Tumors

“…Proposed serum biomarkers include the dysregulated proteins which are released from tumor cells via secretion or unconventional pathways during the development and progression of tumors [ 7 , 8 ]. Additionally, circulating immunoregulatory factors arising from the tumor-immune interplay have been proposed for prognosticating the outcomes of CMT [ 9 ] and related pet animals’ neoplasms [ 10 , 11 ].…”