saline-lavage-for-sampling-of-the-canine-nasal-immune-microenvironment

Saline Lavage for Sampling of the Canine Nasal Immune Microenvironment

Evaluating the local immune microenvironment of the canine nasal cavity can be important for investigating normal tissue health and disease conditions, ...

Colorado State University

Recent studies reported therapeutic effects of Smad7 on oral mucositis in mice without compromising radiation therapy-induced cancer cell killing in neighboring oral cancer. This study aims to assess whether a Smad7-based biologic can treat oral mucositis in a clinically relevant setting by establishing an oral mucositis model in dogs and analyzing molecular targets.

Therapeutic Intervention Using a Smad7-Based Tat Protein to Treat Radiation-Induced Oral Mucositis.

Canine thymomas are routinely treated with radiotherapy (RT). In this study, we investigate the response and toxicity of canine thymoma treated with intensity-modulated stereotactic body radiation therapy (SBRT) relative to dogs treated with hypofractionated non-modulated radiation therapy (NMRT). A retrospective study was performed of dogs with thymoma treated with RT (total: n = 15; SBRT: n = 8, NMRT: n = 7). Tumour response was evaluated in six dogs (40%); following SBRT, three dogs (100%) experienced stable disease (SD); following NMRT, one dog (33%) had a PR, and two dogs (67%) had SD. Median PFS was 116 days (range 66-727 days) for the SBRT group and 134 days (range 10-405 days) for the NMRT group. The MST for the SBRT group was 250 days (range 1-727 days) and 155 days (range 10-405 days) for NMRT. Median disease-specific survival was 250 days (range 1-727 days) for the SBRT group and 169 days (range 20-405 days) for the NMRT group. No significant differences in survival data were found between the treatment groups, however the results from the small number of dogs analysed are likely underpowered for statistical comparisons. Reported acute and late side effects were limited to the lungs and heart and were statistically significantly more common in the NMRT (71%) compared to the SBRT group (25%) (p = .04). We suggest similar treatment efficacy may be provided for canine thymoma treated with either approach, but SBRT could provide the clinical benefit of reduced incidence of radiation-induced toxicity and completion of RT in a shorter time frame.

Outcomes of dogs with thymoma treated with intensity modulated stereotactic body radiation therapy or non-modulated hypofractionated radiation therapy.

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.

Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy.

Intracranial gliomas are the second most common brain tumour in dogs. Radiation therapy provides a minimally invasive treatment option for this tumour type. Earlier publications reporting on the use of non-modulated radiation therapy suggested a poor prognosis for dogs with glioma, with median survival times ranging between 4 and 6 months; more recent literature utilizing stereotactic radiation therapy (SRT) demonstrates that the prognosis for canine gliomas may be more promising, with survival times closer to 12 months. A single institution retrospective study was performed between 2010 and 2020 investigating the outcomes of dogs with biopsy-confirmed glioma or a presumptive diagnosis of intra-cranial glioma based on MRI characteristics that were treated with SRT. Twenty-three client-owned dogs were included. Brachycephalic breeds were overrepresented, totalling 13 dogs (57%). SRT protocols included 16 Gy single fraction (n = 1, 4%), 18 Gy single fraction (n = 1, 4%), 24 Gy in 3 daily fractions (n = 20, 91%), or 27 Gy in four daily fractions (n = 1, 4%). Twenty-one dogs (91%) had improvement of their presenting clinical signs following SRT. Median overall survival time (MST) was 349 days (95% CI, 162-584). Median disease specific survival time was 413 days (95% CI, 217-717). When SRT is incorporated into the management plan for dogs with confirmed or presumed intracranial glioma, a median survival time of approximately 12 months may be achievable.

Erin Trageser

Department of Environmental and Radiological Health Sciences,
College of Veterinary Medicine and Biomedical Sciences,
Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences

Colorado State University

Saline Lavage for Sampling of the Canine Nasal Immune Microenvironment