树突状细胞的成熟信号受到炎症环境和细胞因子（如白细胞介素-6和其下游组分）的抑制。因此，向树突状细胞引入合适的抗原至关重要。然而，减轻抑制性肿瘤微环境的严重程度也是不可或缺的。本研究检验了淋巴细胞抗原6家族成员E（LY6E）波尔斯的成熟树突状细胞（LPMDCs）与吡格列酮联合治疗结直肠癌（CRC），以提高癌症治疗的效果，可能通过吡格列酮在抑制白细胞介素-6/STAT3通路方面发挥作用。树突状细胞源自小鼠骨髓，经淋巴细胞抗原6家族成员E多肽处理后，评估抗原特异性T细胞增殖和Annexin/PI细胞毒性分析。通过实时聚合酶链反应（PCR）在体外评估吡格列酮对白细胞介素（IL）-6/STAT3的影响。然后，通过皮下注射小鼠结肠癌细胞系CT26建立CRC模型，对治疗后的肿瘤、脾脏和淋巴结样本进行组织病理学、ELISA和实时PCR分析。体外结果显示波尔斯的溶菌酶处理树突状细胞对CD3-8双阳性脾细胞增殖和诱导免疫原性细胞死亡反应具有潜力，而吡格列酮则降低了结直肠细胞系中IL-6/STAT3的表达。在动物模型中，接受LPMDCs和吡格列酮联合治疗的受体显示出高水平的肿瘤浸润淋巴细胞。观察到波尔斯的溶菌酶处理树突状细胞和联合治疗组中，IL-12和干扰素-γ（IFN-γ）水平的上升，以及延长的存活期。吡格列酮可以有效改善肿瘤微环境的免疫抑制特征，主要通过IL-6发挥作用。因此，将该药物与LPMDCs联合应用，在挑战肿瘤的动物模型中引发了显著的CD8阳性反应。© 2023 作者。

The maturation faith of dendritic cells is restrained by the inflammatory environment and cytokines, such as interleukin-6 and its downstream component. Therefore, introducing the suitable antigen to dendritic cells is crucial. However, reducing the severity of the suppressive tumor microenvironment is indispensable. The present study examined the combination therapy of lymphocyte antigen 6 family member E (LY6E) pulsed mature dendritic cells (LPMDCs) and pioglitazone against colorectal cancer (CRC) to elevate the effectiveness of cancer treatment through probable role of pioglitazone on inhibiting IL-6/STAT3 pathway.Dendritic cells were generated from murine bone marrow and were pulsed with lymphocyte antigen 6 family member E peptide to assess antigen-specific T-cell proliferation and cytotoxicity assay with Annexin/PI. The effect of pioglitazone on interleukin (IL)-6/STAT3 was evaluated in vitro by real-time polymerase chain reaction (PCR). Afterward, the CRC model was established by subcutaneous injection of CT26, mouse colon carcinoma cell line, in female mice. After treatment, tumor, spleen, and lymph nodes samples were removed for histopathological, ELISA, and real-time PCR analysis.In vitro results revealed the potential of lysate-pulsed dendritic cells in the proliferation of double-positive CD3-8 splenocytes and inducing immunogenic cell death responses, whereas pioglitazone declined the expression of IL-6/STAT3 in colorectal cell lines. In animal models, the recipient of LPMDCs combined with pioglitazone demonstrated high tumor-infiltrating lymphocytes. Elevating the IL-12 and interferon-gamma (IFN-γ) levels and prolonged survival in lysate-pulsed dendritic cell and combination groups were observed.Pioglitazone could efficiently ameliorate the immunosuppressive feature of the tumor microenvironment, mainly through IL-6. Accordingly, applying this drug combined with LPMDCs provoked substantial CD8 positive responses in tumor-challenged animal models.© 2023 The Author(s).