Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM). Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumor-bearing dogs. Ten dogs were enrolled; three dogs did not report any adverse events; three had a mildly altered appetite; one had a mildly increased liver index, while the other three developed suspected anaphylaxis at different levels. The median progression-free interval was 49 days. Dogs with progressive disease during treatment had a shorter survival. This pilot study indicates limited efficacy with potential adverse events of this ACT. Most recruited patients were in a later stage and had macroscopic disease, which might affect the treatment efficacy. Further exploration of this cell therapy in an adjuvant setting, with adequate protocol modification and standardization, could still be considered.

Combination of immunotherapy and radiation therapy has been regarded as a new trend in treating cancers. The purpose of this study was to evaluate safety and peripheral blood lymphocyte changes in dogs diagnosed with oral malignant melanoma who received an immunotherapeutic dendritic cell vaccine and concurrent radiotherapy. The vaccine was conducted by fusing allogeneic dendritic cells and autologous tumor cells and was administrated subcutaneously every two weeks. Concurrent hypofractionated radiotherapy was given weekly. Six dogs were enrolled in this pilot clinical study. The treatment was well-tolerated, with only mild radiotherapy-related side effects reported. The median progression-free survival was 146.5 days. Flow cytometrical analysis of the peripheral blood lymphocyte revealed a decreased CD4/CD8 ratio in only one dog, who was also the only long-term survivor. The study provides insights into immune cell changes during immuno-radiotherapy and also supports further expansion of this kind of treatment, investigation of treatment efficacy, and exploration of correlations between immune cell changes and outcome.

YKL-40, a secretory glycoprotein, is known as a prognostic biomarker in human cancers, but its role in canine multicentric lymphoma is not well understood. This study aimed to investigate serum YKL-40 levels in thirty dogs with multicentric lymphoma to determine their prognostic value, association with patient characteristics, and potential to predict chemotherapy response. Serum samples were collected before, during, and after chemotherapy, and YKL-40 level was measured using ELISA. The results showed that the pretreatment serum YKL-40 levels were significantly higher in dogs with multicentric lymphoma (394.0 pg/mL, n = 30) than in healthy controls (218.6 pg/mL, n = 11) (p = 0.012). While a cutoff value of 445.1 pg/mL was observed, further studies are needed to clarify its diagnostic utility. Dogs with clinical stage V had the highest YKL-40 levels (p = 0.027), potentially reflecting disease severity. Furthermore, YKL-40 levels decreased after chemotherapy (p = 0.030). However, YKL-40 levels showed no significant association with progression-free survival (PFS) (HR = 0.93, p = 0.830) or overall survival (OS) (HR = 0.99, p = 0.267). In conclusion, serum YKL-40 levels may potentially detect the disease severity, but its prognostic role remains uncertain. Further studies are required to evaluate serum YKL-40 levels as a potential indicator of treatment response or disease recurrence.