Dataset Information

An HNSCC syngeneic mouse model for tumor immunology research and preclinical evaluation.

ABSTRACT: The lack of reliable animal models to assess the safety and efficacy of drugs and to explore the underlying molecular mechanisms is one of the most severe impediments in head and neck squamous cell carcinoma (HNSCC) tumor immunology research. The majority of xenograft tumor models established using immunodeficient mice neglect the effects of T cells. To date, to the best of our knowledge, there is no syngeneic tumor model available that reflects the immune microenvironmental features of HNSCC tumors. To solve this issue, the present study used 4?nitroquinoline?1?oxide (4?NQO) to induce squamous cell carcinoma in C57BL/6 mice. Three HNSCC cell lines were then established, and one of these, termed JC1, was selected for further analysis due to its enhanced proliferative ability and tumorigenicity in immunodeficient nude mice. However, none of the 3 cell lines could form tumors in immunocompetent mice. Due to the different tumorigenicities in nude and C57BL/6 mice, the immune system may play an important role in inoculated JC1 tumor progression. Chemical induction was used to establish the tumorigenicity?enhanced cell line, JC1?2, which can form syngeneic tumors in immunocompetent C57BL/6 mice. Next?generation sequencing (NGS) was used to perform the immunogenomic and transcriptomic characterization of the JC1?2 cells. Splenocytes were isolated from C57BL/6 mice and co?cultured with JC1?2 cells to verify the responsiveness of the interferon (IFN)?? pathway in the JC1?2 cell line. Unlike the majority of syngeneic mouse tumors, the JC1?2?formed tumors resembled 'inflamed tumors' due to the abundancy of immune cells in the tumor microenvironment. Moreover, more intense immune responses were observed in the orthotopic mouse model than in the heterotopic model. Thus, this model could be used to delineate the interactions between HNSCC and lymphocytes, and to validate novel immunotherapy targets.

SUBMITTER: Fu Y

PROVIDER: S-EPMC7447356 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An HNSCC syngeneic mouse model for tumor immunology research and preclinical evaluation.

Fu You Y Tian Guocai G Li Jiang J Zhang Zhiyuan Z Xu Ke K

International journal of molecular medicine 20200722 4

The lack of reliable animal models to assess the safety and efficacy of drugs and to explore the underlying molecular mechanisms is one of the most severe impediments in head and neck squamous cell carcinoma (HNSCC) tumor immunology research. The majority of xenograft tumor models established using immunodeficient mice neglect the effects of T cells. To date, to the best of our knowledge, there is no syngeneic tumor model available that reflects the immune microenvironmental features of HNSCC tu ...[more]

PMID: 32700748

Similar Datasets

Project description:We have identified a mechanism by which cytomegalovirus (CMV) interleukin-10 (IL-10) is utilized by glioblastoma multiforme (GBM) to maintain the immunosuppressive microenvironment. CMV has been ubiquitously detected within high-grade gliomas, but its role has not been fully elicited. GBMs harvested ex vivo were analyzed by flow cytometry to determine CMV antigen expression. Distinct expressing subsets of cells, such as the myeloid lineage and CD133+ cells, were identified. CMV antigens US28, pp65, IE1, and gB were also present within four individual and fully characterized human GBM-derived glioma cancer stem cell (gCSC) populations as ascertained by flow cytometry. These gCSCs produce CMV IL-10 in a range from 5.62 to 111.11 pg/mL/106cells/day. When human CD14+ monocytes, precursor cells to macrophages/microglia, were exposed to gCSC-conditioned medium or recombinant CMV IL-10, there was a marked increase in the expression of immune-suppressive factors such as B7-H1, p-STAT3, VEGF, and TGF-beta. Concurrently, anti-tumor and pro-immune MHC II and CD86 were down-regulated and the expression pattern of immune markers was similar to the phenotype of glioma-associated macrophages/microglia. Exposure of CD14+ cells to CMV IL-10 induced the up-regulation of IE1, a marker of transcriptional activity of CMV. Chemotaxis assays revealed that the supernatant from CD14+ cells exposed to CMV IL-10 was able to induce the migration of gCSCs compared with the supernatant from CD14+ cells cultured in medium alone. This result indicates that CMV subverts GBM-associated macrophages/microglia to support the immune-suppressive microenvironment by shifting their phenotype to the immune-suppressive M2. The shift is subsequent to activation of the STAT3 pathway, resulting in the propagation of glioma angiogenesis via an increase in VEGF and by increasing glioma invasion. Therapeutic strategies involving immune-mediated cytotoxic responses now include strategies to reverse tumor-mediated immune suppression. This study suggests that including CMV as a target could enhance the effectiveness of immunotherapy.

Dataset Information

An HNSCC syngeneic mouse model for tumor immunology research and preclinical evaluation.

Publications

An HNSCC syngeneic mouse model for tumor immunology research and preclinical evaluation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets