CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Attenuated Toxoplasma gondii enhances the antitumor efficacy of anti-PD1 antibody by altering the tumor microenvironment in a pancreatic cancer mouse model.
Attenuated Toxoplasma gondii enhances the antitumor efficacy of anti-PD1 antibody by altering the tumor microenvironment in a pancreatic cancer mouse model.
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这些发现可能提供一种新的免疫治疗途径，用于治疗 PDAC 实体瘤并克服 PDAC 肿瘤对抗 PD-1 药物的耐药性。
探讨减毒弓形虫对胰腺癌实体瘤是否有效，以及减毒弓形虫是否能提高αPD-1抗体对胰腺癌的抗肿瘤活性。
研究了减毒弓形虫NRTUA株单药治疗以及NRTUA与抗PD-1抗体联合治疗对Pan02荷瘤小鼠PDAC肿瘤体积和肿瘤重量的治疗效果。我们通过免疫组织化学、流式细胞术和ELISA，表征了NRTUA与抗PD-1抗体联合治疗对TIL（肿瘤浸润淋巴细胞）和肿瘤特异性IFN-γ的影响。通过清除CD8+ T细胞和IL-12，研究了NRTUA与抗PD-1抗体联合治疗的抗肿瘤机制。
NRTUA 菌株治疗通过激活树突状细胞并增加肿瘤微环境中 CD8+ T 细胞浸润，在 PDAC 皮下小鼠模型中抑制了肿瘤生长。更重要的是，NRTUA 与 anti-PD-1 抗体联合治疗引发了显著的抗肿瘤免疫反应，并在 Pan02 荷瘤小鼠中协同控制肿瘤生长。具体而言，联合治疗导致由树突状细胞分泌的 IL-12 介导的 CD8+ T 细胞浸润增加，并在 PDAC 肿瘤微环境中产生肿瘤特异性 IFN-γ。此外，联合治疗显著减少了 PDAC 小鼠中具有免疫抑制作用的髓源性抑制细胞群体。
To investigate whether attenuated Toxoplasma is efficacious against solid tumors of pancreatic cancer and whether attenuated Toxoplasma improves the antitumor activity of αPD-1 antibody on pancreatic cancer.
The therapeutic effects of attenuated Toxoplasma NRTUA strain monotherapy and combination therapy of NRTUA with anti-PD-1 antibody on PDAC tumor volume and tumor weight of Pan02 tumor-bearing mice were investigated. We characterized the effects of combination therapy of NRTUA with anti-PD-1 antibody on tumor-infiltrating lymphocytes and tumor-specific IFN-γ by using immunohistochemistry, flow cytometry and ELISA. The antitumor mechanisms of combination therapy of NRTUA with anti-PD-1 antibody were investigated via depletion of CD8 + T cells and IL-12.
NRTUA strain treatment inhibited tumor growth in a subcutaneous mouse model of PDAC through activating dendritic cells and increasing CD8 + T cell infiltration in the tumor microenvironment. More importantly, combination therapy of NRTUA with anti-PD-1 antibody elicited a significant antitumor immune response and synergistically controlled tumor growth in Pan02 tumor-bearing mice. Specifically, the combination treatment led to elevation of CD8 + T cell infiltration mediated by dendritic cell-secreted IL-12 and to tumor-specific IFN-γ production in the PDAC tumor microenvironment. Also, the combination treatment markedly reduced the immunosuppressive myeloid-derived suppressor cell population in PDAC mice.
These findings could provide a novel immunotherapy approach to treating solid tumors of PDAC and overcoming resistance to anti-PD-1 agents in PDAC tumors.
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