Transcriptome analyses of tumor-infiltrating dendritic cells (TIDC) from WT versus Tsc22d3 conditional knockout (Tsc22d3-cKO) mice under stress and chemotherapy conditions

In this context (Stress and MTX-based chemotherapy of established tumors), TIDC were purified from WT and Tsc22d3-cKO mice, followed by RNAseq-based transcriptome analyses . The absence of Tsc22d3 favored the upregulation of IFN-β stimulated genes in TIDC , indicating that Tsc22d3 acts to repress the type I IFN response, which is known to be required for anticancer immunosurveillance. Interestingly, the SD-inhibited expression of several genes involved in MHC I-restricted antigen presentation was partially reversed (Calr, Sec61b, Sec61g) in Tsc22d3-deficient TIDC . However, the expression of TLRs, antigen uptake and cell adhesion molecules, chemokines/cytokines and receptors (except Ifnb1 and Ccl5) remained largely unchanged in TIDC lacking Tsc22d3, compared with their WT counterparts.

本研究场景聚焦于实体瘤的应激与甲氨蝶呤（MTX）化疗。研究人员从野生型（Wild Type, WT）及Tsc22d3条件性敲除（Tsc22d3-cKO）小鼠体内纯化得到肿瘤浸润树突状细胞（Tumor-Infiltrating Dendritic Cells, TIDC），随后开展基于RNA测序（RNA sequencing, RNAseq）的转录组分析。Tsc22d3的缺失可促进肿瘤浸润树突状细胞中干扰素β（IFN-β）刺激基因的上调，这表明Tsc22d3能够抑制I型干扰素应答——而I型干扰素应答已被证实是抗肿瘤免疫监视所必需的关键过程。值得注意的是，在Tsc22d3缺陷的肿瘤浸润树突状细胞中，数种参与主要组织相容性复合体I类（Major Histocompatibility Complex class I, MHC I）限制性抗原呈递的基因的SD抑制表达得到了部分逆转，涉及钙网蛋白基因（Calr）、Sec61亚基β基因（Sec61b）与Sec61亚基γ基因（Sec61g）。不过，与野生型对照相比，Tsc22d3缺陷的肿瘤浸润树突状细胞中，Toll样受体（Toll-like Receptors, TLRs）、抗原摄取与细胞黏附分子、趋化因子/细胞因子及其受体（Ifnb1与Ccl5除外）的表达基本未发生显著改变。