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

Abstract

Despite the important role of preclinical experiments to characterize tumor biology and molecular pathways, there are ongoing challenges to model the tumor microenvironment, specifically the dynamic interactions between tumor cells and immune infiltrates. Comprehensive models of host-tumor immune interactions will enhance the development of emerging treatment strategies, such as immunotherapies. Although in vitro and murine models are important for the early modelling of cancer and treatment-response mechanisms, comparative research studies involving veterinary oncology may bridge the translational pathway to human studies. The natural progression of several malignancies in animals exhibits similar pathogenesis to human cancers, and previous studies have shown a relevant and evaluable immune system. Veterinary oncologists working alongside oncologists and cancer researchers have the potential to advance discovery. Understanding the host-tumor-immune interactions can accelerate drug and biomarker discovery in a clinically relevant setting. This review presents discoveries in comparative immuno-oncology and implications to cancer therapy.

Bridging clinic and wildlife care with AI-powered pan-species computational pathology

“…Here, we demonstrated the clinical utility of immune scoring based on routine H&E samples, representing a cost-effective and streamlined solution for risk stratification, much like initiatives in human cancers 54 , 55 . This is also particularly important for animal cancer management 56 , because of the limitation in resource and cost constraint, for example, owners of companion animals may not want to consider tests with high costs. In addition, our finding resonates with recent discoveries in human cancers that the spatial context of immune cells is crucial to cancer development and response to therapy 30 , 40 , 54 , 57 , 58 .…”

The Integration of Community-Dwelling Non-Human Companion Animals in Research Programs

“…Comparative oncology reviews (Anderson & Modiano, 2015;Beck et al, 2022;Bentley et al, 2017;Burton & Khanna, 2014;Dias et al, 2021;Finocchiaro & Glikin, 2017;Garden et al, 2018;Gardner et al, 2016;Gingrich et al, 2019;Giuliano, 2021;Gordon & Khanna, 2010;Kieslinger et al, 2019;Kleber et al, 2022;LeBlanc & Mazcko, 2020;Lollini et al, 2013;Mestrinho & Santos, 2021;Nickoloff et al, 2017;Oh & Cho, 2023;Page et al, 2016;Pinard et al, 2022;Porrello et al, 2004Porrello et al, , 2006Rahman et al, 2023;Regan et al, 2018;Riccardo et al, 2015;Vafaei et al, 2022;Vail & Thamm, 2000.;Vanhaezebrouck & Scarpelli, 2023;Withers et al, 2019;Withrow & Wilkins, 2010) Cell therapy review (Arzi et al, 2021) Thesis (Gruen, 2016) Ethical review (Bertout et al, 2021) One Health reviews (Arzi et al, 2022;Kol et al, 2015) Perianal fistulas review (Burdzinska et al, 2022) Osteoarthritis (Cimino Brown, 2017) Pain reviews (Iadarola et al, 2021;Lascelles et al, 2018Lascelles et al, , 2022 Cachex...…”

PDL1 immunohistochemistry in canine neoplasms: Validation of commercial antibodies, standardization of evaluation, and scoring systems

“…The International Immuno-Oncology Biomarker Working Group has recently recognized the value of comparatively studying tumor-infiltrating lymphocytes and immuno-oncology in domestic animals as a spontaneous model for humans. 26 Programmed cell death protein 1 (PD1) is an inhibitory receptor belonging to the CD28 family and is mainly expressed in activated T lymphocytes. Its ligand, programmed cell death ligand 1 (PDL1), is expressed in various cell types, including cells of the hematopoietic system, which interact with T lymphocytes through the PD1/PDL1 immune checkpoint axis, inducing immune modulation and preventing an excessive effector response.…”

“…The International Immuno-Oncology Biomarker Working Group has recently recognized the value of comparatively studying tumor-infiltrating lymphocytes and immuno-oncology in domestic animals as a spontaneous model for humans. 26…”