Immune Phenotypic Characterization of a TRAIL-Knockout Mouse

• Published in: Cancers Vol. 15; no. 5; p. 1475
• Main Authors: Stoyanova, Ani K, Sattler, Arne, Hahn, Elisabeth M, Hering, Nina A, Arndt, Marco, Lauscher, Johannes Christian, Speichinger-Hillenberg, Fiona, Kotsch, Katja, Berg, Ann-Kathrin, Beyer, Katharina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.02.2023; MDPI
• Subjects: Analysis; Antibodies; Apoptosis; CD122 antigen; CD3 antigen; CD4 antigen; CD8 antigen; Cell proliferation; Dendritic cells; Effector cells; Flow cytometry; Genotype & phenotype; Immune system; Immunological memory; Immunology; Lymphatic system; Lymphocytes; Lymphocytes T; Memory cells; Methods; Pancreatic carcinoma; Phenotype; Phenotypes; Signal transduction; Spleen; Therapeutic targets; TRAIL protein; Tumor cells; Tumor necrosis factor; Tumors; Germany; United States > US; dendritic cells; lymphocytes; TRAIL: immunological phenotype; knockout mouse
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15051475

The TNF-superfamily member TRAIL is known to mediate selective apoptosis in tumor cells suggesting this protein as a potential antitumor drug target. However, initial successful pr-clinical results could not be translated into the clinic. Reasons for the ineffectiveness of TRAIL-targeting in tumor therapies could include acquired TRAIL resistance. A tumor cell acquires TRAIL resistance, for example, by upregulation of antiapoptotic proteins. In addition, TRAIL can also influence the immune system and thus, tumor growth. We were able to show in our previous work that TRAIL mice show improved survival in a mouse model of pancreatic carcinoma. Therefore, in this study we aimed to immunologically characterize the TRAIL mice. We observed no significant differences in the distribution of CD3 , CD4 , CD8 T-cells, Tregs, and central memory CD4 and CD8 cells. However, we provide evidence for relevant differences in the distribution of effector memory T-cells and CD8 CD122 cells but also in dendritic cells. Our findings suggest that T-lymphocytes of TRAIL mice proliferate at a lower rate, and that the administration of recombinant TRAIL significantly increases their proliferation, while regulatory T-cells (Tregs) from TRAIL mice are less suppressive. Regarding the dendritic cells, we found more type-2 conventional dendritic cells (DC2s) in the TRAIL mice. For the first time (to the best of our knowledge), we provide a comprehensive characterization of the immunological landscape of TRAIL-deficient mice. This will establish an experimental basis for future investigations of TRAIL-mediated immunology.