Metastasized murine oral squamous cell carcinoma cells induce intratumoral polymorphonuclear myeloid derived suppressor cells

Abstract

Myeloid derived suppressor cells (MDSCs) localize to hematopoietic organs and peripheral blood during inflammation or tumor tissues and lymph nodes in the presence of a tumor. However, whether there are differences in MDSCs found in the primary tumor and metastases is unknown. In the present study, we established a cell line of metastasized tumor cells to a lymph node, L5-11, which were derived from the Sq-1979 mouse buccal mucosa squamous cell carcinoma cell line. We then analyzed tumor immunogenicity, especially with regard to MDSCs, to clarify the differences between the primary tumor and metastases, using an isogenic heterotopic tumor transplantation model. Our data showed that the population of intratumoral MDSCs, especially polymorphonuclear MDSCs in the lymph node metastasis model were significantly increased compared with syngeneic grafts from the primary cell line Sq-1979 after 21 days. Furthermore, we identified that the lymph node metastasis cell line had increased expression of genes that promote the expansion of MDSCs, tumor growth and metastasis. Hence, these data suggest that tumor immunosuppression can occur via activation of MDSCs. However, further examination is required to clarify whether all or a subset of these factors from the lymph node metastasis tumor cells are required to induce intratumoral MDSCs.

The Role of Immune Modulatory Cytokines in the Tumor Microenvironments of Head and Neck Squamous Cell Carcinomas

“…M-MDSCs secreted factors, including IL-6, IL-1β, IL-23, and PGE2, and facilitated Th17 cell differentiation [ 102 ]. Syngeneic mouse OSCC models have also demonstrated the preferential activation of PMN-MDSC in metastasized OSCC tissues [ 103 ]. The PMN-MDSCs elevated in OSCC patients can exert strong immunosuppressive effects, via p-STAT3/reactive oxygen species, as well as abrogated T cell proliferation and IFN-γ production [ 104 ].…”

Tumor immune microenvironment in head and neck cancers

“…Previous studies suggest that MDSC may play a pivotal role in predicting tumor response to various tumor immunotherapies 14,65,73–76 . MDSCs circulate in peripheral blood, draining lymphoid tissue, as well as in HNSCC tumor tissue 77–79 . Many studies have demonstrated that MDSCs downregulate immune responses during infection, inflammation, and tumor development 14,67,79–85 .…”

“…14,65,[73][74][75][76] MDSCs circulate in peripheral blood, draining lymphoid tissue, as well as in HNSCC tumor tissue. [77][78][79] Many studies have demonstrated that MDSCs downregulate immune responses during infection, inflammation, and tumor development. 14,67,[79][80][81][82][83][84][85] MDSCs are CD11b + cells that are phenotypically subdivided into two groups, polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC).…”

Perspectives of Immune Suppression in the Tumor Microenvironment Promoting Oral Malignancy

“…In order to compare the immune-modulatory effects of OSCCs in primary and advanced stages, we have established a metastasized model (L5-11cells) representing more malignant phenotypes than the parental OSCC (Sq-1979 cells) when implanted in the syngeneic mice [ 82 ]. Our results revealed that it is metastasized L5-11 cells, not early-stage Sq-1979 cells that predominantly induce PMN-MDSCs in tumor-bearing mice [ 83 ]; this is not simply reflecting the differential tumor size, since even the larger amount of inoculation of Sq1979 cells could not induce the MDSC cells in the mice. We have also confirmed that the quantity of IFN-γ produced by stimulated spleen cells is significantly suppressed in mice implanted with Sq-1979 and L5-11 cells; however, the production of IL-10 is significantly elevated in mice implanted with Sq-1979 while markedly suppressed in L5-11 cell-implanted mice [ 84 ].…”

“…Potentiated CAF could also affect other immune-suppressive mediators such as Treg, TAM and MDSCs. In the advanced stage, MDSCs could possibly be a major conductor of immune-suppression [ 83 ]. In the TME, the effector Treg, harboring CCR6, PD-1 and CTLA-4, could be mobilized by antigens and/or chemokines secreted from OSCC cells.…”