Introduction

The recent success using immunotherapy to cure cancer has considerably renewed the interest for research in tumor immunology. Compared to conventional cancer treatments with radiation therapy and chemotherapy, immunotherapy is far less damaging to the body and has less detrimental side effects. In addition, promoting patients’ own defenses and enhancing tumor immunity is more likely to prevent cancer relapse. Among the current operational immunotherapeutic methods used, one can mention the adoptive cell transfer with engineered T cells transformed in vitro to express chimeric antigen receptors. This type of active treatment is very effective and now increasingly used against blood cancers or leukemia. The development immune stimulating immunotherapy is a more recent type of treatment. It has led to remarkable clinical effects as illustrated by the famous complete cure of metastatic melanoma of former president of United States of America Jimmy Carter. This approach uses humanized antibodies that block the checkpoint inhibitors CTLA-4 and PD1, of two important immune pathways. The blockade of these inhibitory receptors enhances antitumor T cell response by preventing or abrogating suppressive signals. Despite undeniable successes, the clinical application of immunotherapy remains challenging and very expensive. As such, there is a need for improving current strategies as well as for developing novel ones. While this endeavor heavily and almost exclusive relies on murine models, a wider comparative approach using less conventional animal models may be helpful. Indeed, studies over many years have revealed that cancerous diseases are widely found not only in vertebrates but also in invertebrates (reviewed in Aktipis et al. 2015; Robert, 2010).

Given the renewed attention for tumor immunology, it seems appropriate and timely to inform and educate the mainstream biomedical community about tumorigenesis and tumor immunity across the whole animal kingdom. This would provide a broader view of unappreciated attractive animal models and comparative approaches alternative to mice.

Thus, in this special thematic issue of our journal Immunological Investigations, we present alternative ways either using human cell lines or non-murine animals to gathering further insights into host-tumor interactions. In a first paper, Young Zen (2019) explores the generation of splicing variants of a serine protease homolog known to be important for tumor invasion in an invertebrate arthropod (the Crayfish, Procambarus clarkii). This is followed by two papers (Li et al., 2019; Owen and Siddle, 2019) concerning the interesting case of the Devil Facial Tumor Disease (DFTD) that plague the Tasmanian Devil, a mammalian species of Tasmania. This is a fatal monophyletic clonally transmissible cancer type that spreads between devils by biting during fights for mating. Xinying Li et al. (2019) have investigated whether murine macrophage cell lines can phagocytize Devil Facial Tumor Disease (DFTD1) cancer cells in vitro and if so whether TNF tumor necrosis factor (TNF) alpha would be critically involved. Given the MHC class I deficiency interfering with anti-DFTD tumor CD8 T cell cytotoxicity, the possible role of antibody-mediated phagocytosis is a potentially relevant mechanism to explore. The second paper by Owen and Siddle (2019) is a comprehensive and timely review on the Devil facial tumors emphasizing the recent progress in anti-DFTP vaccine development. The review also provides an update of a second more recently discovered transmissible cancer in Tasmanian Devils (DFDT2). We then move to amphibians with a review by Banach and Robert (2019) on the recent progress and challenges using innate-like T cells such as NKT cells for cancer immunotherapy, and then presenting an alternative model to mice for gathering better fundamental understanding of the role of innate-like T cells in cancer. This special issue ends on the other side of the spectrum with two papers using human cell lines as proxy. Kazemi-Sefat et al. (2019) have assessed the effects of histone deacetylase inhibitor sodium butyrate on expression of toll-like receptor 4 in several human-derived colorectal tumor cell lines. Their innovative rationale is that sodium butyrate released by gut bacteria may be involved in tumorigenesis. Then, Lili Wang et al. (2019) have evaluated the potential use of immunoglobulin-like transcript 4 as an additional marker of dendritic cell subset in the context of hepatocellular carcinoma.

Overall, we hope that this special issue will stimulate interest in comparative study of cancer immunology and encourage researcher to diversify, using animal models which are alternative to mice.