Dataset Information

Comparative analysis of tumor-infiltrating lymphocytes in a syngeneic mouse model of oral cancer.

ABSTRACT: OBJECTIVE:To perform a comparative analysis of infiltrating immune cells in a newly developed C57BL/6 background syngeneic transplantable mouse oral cancer (MOC) model. STUDY DESIGN/SETTING:Scientific study in an academic medical center. METHODS:Use of carcinogen-induced tumorigenesis, tissue culture, cell line transplantation, and flow cytometric analysis techniques. RESULTS:Previously, the authors established a series of cell line models that displayed dichotomous growth phenotypes when transplanted into immunocompetent mice. They now show that the indolent growth pattern of the MOC1-generated tumors is associated with increased baseline and inducible major histocompatibility complex class I expression and increased CD8(+) T-cell infiltration into the tumor microenvironment. Conversely, the aggressive and metastatic pattern of MOC2-generated tumors has decreased basal and inducible class I expression and is associated with FOXP3(+)CD4(+) regulatory T-cell infiltration. Delayed primary tumor growth after targeted monoclonal antibody therapy of these FOXP3(+) regulatory cells further suggests that these immune cells contribute to the aggressive phenotype of MOC2. CONCLUSION:These data validate that key infiltrating immune cells identified here parallel findings in human head and neck cancer, making this newly developed syngeneic model a critical platform for the continued dissection of tumor-host interactions in head and neck cancer.

SUBMITTER: Judd NP

PROVIDER: S-EPMC6346425 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Comparative analysis of tumor-infiltrating lymphocytes in a syngeneic mouse model of oral cancer.

Judd Nancy P NP Allen Clint T CT Winkler Ashley E AE Uppaluri Ravindra R

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 20120319 3

<h4>Objective</h4>To perform a comparative analysis of infiltrating immune cells in a newly developed C57BL/6 background syngeneic transplantable mouse oral cancer (MOC) model.<h4>Study design/setting</h4>Scientific study in an academic medical center.<h4>Methods</h4>Use of carcinogen-induced tumorigenesis, tissue culture, cell line transplantation, and flow cytometric analysis techniques.<h4>Results</h4>Previously, the authors established a series of cell line models that displayed dichotomous ...[more]

PMID: 22434099

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Project description:Murine syngeneic tumor models have been used extensively for cancer research for several decades and have been instrumental in driving the discovery and development of cancer immunotherapies. These tumor models are very simplistic cancer models, but recent reports have, however, indicated that the different inoculated cancer cell lines can lead to the formation of unique tumor microenvironments (TMEs). To gain more knowledge from studies based on syngeneic tumor models, it is essential to obtain an in-depth understanding of the cellular and molecular composition of the TME in the different models. Additionally, other parameters that are important for cancer progression, such as collagen content and mechanical tissue stiffness across syngeneic tumor models have not previously been reported. Here, we compare the TME of tumors derived from six common syngeneic tumor models. Using flow cytometry and transcriptomic analyses, we show that strikingly unique TMEs are formed by the different cancer cell lines. The differences are reflected as changes in abundance and phenotype of myeloid, lymphoid, and stromal cells in the tumors. Gene expression analyses support the different cellular composition of the TMEs and indicate that distinct immunosuppressive mechanisms are employed depending on the tumor model. Cancer-associated fibroblasts (CAFs) also acquire very different phenotypes across the tumor models. These differences include differential expression of genes encoding extracellular matrix (ECM) proteins, matrix metalloproteinases (MMPs), and immunosuppressive factors. The gene expression profiles suggest that CAFs can contribute to the formation of an immunosuppressive TME, and flow cytometry analyses show increased PD-L1 expression by CAFs in the immunogenic tumor models, MC38 and CT26. Comparison with CAF subsets identified in other studies shows that CAFs are skewed towards specific subsets depending on the model. In athymic mice lacking tumor-infiltrating cytotoxic T cells, CAFs express lower levels of PD-L1 and lower levels of fibroblast activation markers. Our data underscores that CAFs can be involved in the formation of an immunosuppressive TME.

Dataset Information

Comparative analysis of tumor-infiltrating lymphocytes in a syngeneic mouse model of oral cancer.

Publications

Comparative analysis of tumor-infiltrating lymphocytes in a syngeneic mouse model of oral cancer.

Similar Datasets

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