This association was even stronger than that observed for cytotoxic CD8 + T cells, highlighting the anti-tumor effect of cells in the TME (Gentles et al., 2015). Unique T cells have been observed in teleosts and characterized in zebrafish. microenvironment (TME) of teleosts. In addition, we summarize zebrafish models developed for the study of malignancy and adaptive immunity along with other available tools and technology afforded by this experimental system. Finally, we discuss some recent research carried out using the zebrafish to investigate adaptive immune cell-tumor interactions. Without a doubt, the zebrafish will arise as one of the traveling forces to help expand the knowledge of tumor immunity Raphin1 and facilitate the development of improved anti-cancer immunotherapy in the foreseeable future. in the erythroid lineage and in the myeloid lineage (Yamada et al., 2001; Dooley et al., 2005; Galloway et al., 2005; Zhu et al., 2005; Yang et al., 2019). Lymphoid cell development follows immediately after the appearance of erythroid and myeloid cells, similar to what has been observed at CS11 or 24 days post-conception in humans (Herbomel et al., 1999; Tavian et al., 2010; Carroll and North, 2014; Ivanovs et al., 2017). Markers of lymphoid progenitors, such as expression under the tumor necrosis factor-alpha promoter to identify and visually track M1 (mCherry+; eGFP+) and M2 (mCherry+; eGFP-) macrophages in zebrafish (Nguyen-Chi et al., 2015). Moreover, upon induced swelling through fin-wounding, tumor transplantation, or inoculation, zebrafish M1 and M2 macrophages recapitulate the activation and gene manifestation patterns as founded in higher vertebrates (Nguyen-Chi et al., 2015; Sanderson et al., 2015; Hasegawa et al., 2017; Nguyen-Chi et al., 2017; Tsarouchas et BSG al., 2018). Related to what is definitely observed in humans, zebrafish neutrophils possess polymorphic nuclei, granules, and myeloid-specific peroxidase coupled with NADPH oxidase (Lieschke et al., 2001; Henry et al., 2013). Taken together, the presence of DCs, macrophages, and neutrophils in zebrafish and their similarities to humans make the zebrafish appropriate to study innate immunity and their relationships with adaptive immune cells in the TME. T Lymphocytes T lymphocytes are Raphin1 the major players in tumor immunity and include different subtypes characterized by their respective functions. Cytotoxic CD8 + T cells have become probably one of the most analyzed subtypes due to the recent success in checkpoint blockade therapies focusing on CTLA-4 and PD-L1 signaling pathways (Gong et al., 2018). The anti-tumor response of CD8+T cells is definitely canonically supported by CD4+Th1 helper cells (Ostroumov et al., 2018). Additionally, the TME also harbors additional subtypes of CD4 + T lymphocytes, including Th2, Th17, and CD4 + /Foxp3 + Tregs that aid in immune evasion in most tumors (Speiser et al., 2016). T lymphocyte profiles within the TME of solid tumors Raphin1 vary greatly among individuals. The ratio of one subtype versus another can forecast treatment outcome and rates of disease relapse (Fridman et al., 2012). With related subtypes and functions of T lymphocytes (Zhang and Wiest, 2016; Bajoghli et al., 2019), the zebrafish represents a useful model to facilitate understanding of the interplay among T lymphocyte subtypes within the TME. Translating this knowledge to the bedside can help improve immunotherapy and patient prognosis. Cytotoxic CD8 + T Cells Cytotoxic CD8 + T cells are derived from the lineage of T-cell receptors (TCR) and identify antigens offered by MHC-I molecules, serving as a major immune surveillance guard against tumors. Elevated numbers of triggered CD8 + T cells within the TME are associated with positive results among individuals with breast malignancy, colorectal malignancy, renal malignancy, and melanoma (Clemente et al., 1996; Tosolini et al., 2011; Gu-Trantien et al., 2013; Bohner et al., 2019; Ye et al., 2019). Cytotoxic CD8 + T cells identify Raphin1 tumor antigens and actually participate tumor cells through spatial proximity to Raphin1 remove them (Pittet, 2009). Two main pathways are involved in this process: (1) granule exocytosis through the family of serine proteases: the.