RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The Combination of CD300c Antibody with PD-1 Blockade Suppresses Tumor Growth and Metastasis by Remodeling the Tumor Microenvironment in Triple-Negative Breast Cancer.
The Combination of CD300c Antibody with PD-1 Blockade Suppresses Tumor Growth and Metastasis by Remodeling the Tumor Microenvironment in Triple-Negative Breast Cancer.
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三阴性乳腺癌(TNBC)是一种侵袭性癌症,具有高复发风险、侵袭性、转移潜能和不良预后等特征。肿瘤相关巨噬细胞(TAMs),尤其是M2样TAMs,通过促进免疫抑制性肿瘤微环境(TME)来推动TNBC进展,凸显了TME重塑的必要性。
本研究旨在评估联合使用CL7(一种诱导M1巨噬细胞极化的CD300c单克隆抗体)和抗PD-1(一种免疫检查点抑制剂)在TNBC中的治疗效果。为建立TNBC模型,将4T1细胞接种至小鼠左侧第四乳腺。CL7和抗PD-1每周静脉给药两次。采用流式细胞术和RT-PCR评估免疫治疗效果,并通过肺组织苏木精-伊红染色评估肺转移。与PBS组和单药治疗组相比,联合治疗组(CL7和抗PD-1)的肿瘤生长显著减少。
此外,联合治疗增加了肿瘤中的M1巨噬细胞以及活化的CD8+ T细胞和NK细胞,同时显著抑制了肺转移。这些发现表明,CL7和抗PD-1的联合治疗具有通过重塑TME来治疗TNBC的潜力。
Triple-negative breast cancer (TNBC) is an aggressive cancer characterized by a high risk of recurrence, invasiveness, metastatic potential, and poor prognosis. Tumor-associated macrophages (TAMs), particularly M2-like TAMs, contribute to TNBC progression by promoting an immunosuppressive tumor microenvironment (TME), highlighting the need for TME remodeling.
This study aimed to evaluate the therapeutic efficacy of co-administering CL7, a CD300c monoclonal antibody that induces M1 macrophage polarization, and anti-PD-1, an immune checkpoint inhibitor, in TNBC. To establish a TNBC model, 4T1 cells were inoculated into the fourth left mammary gland of mice. CL7 and anti-PD-1 were intravenously administered twice a week.
Flow cytometry and RT-PCR were performed to assess the immunotherapeutic effects, and lung metastases were evaluated by the Hematoxylin and Eosin staining of lung tissues. Tumor growth was significantly reduced in the combination treatment group (CL7 and anti-PD-1) compared to both the PBS and monotherapy groups.
Additionally, the combination treatment increased M1 macrophages and activated CD8+ T and NK cells in the tumor, while significantly suppressing lung metastases.
These findings suggest that the combination of CL7 and anti-PD- therapy has the potential to treat TNBC by remodeling the TME.
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