PDF(Pubmed)
Abstract：
UNASSIGNED: Immunotherapy is revolutionizing the management of multiple cancer types. However, only a subset of patients responds to immunotherapy. One mechanism of resistance is the absence of immune infiltrates within the tumor. In situ vaccine with local means of tumor destruction that can induce immunogenic cell death have been shown to enhance tumor T cell infiltration and increase efficacy of immune checkpoint blockade.
UNASSIGNED: Here, we compare three different forms of localize tumor destruction therapies: radiation therapy (RT), vascular targeted photodynamic therapy (VTP) and cryoablation (Cryo), which are known to induce immunogenic cell death, with their ability to induce local and systemic immune responses in a mouse 4T1 breast cancer model. The effects of combining RT, VTP, Cryo with anti-PD1 was also assessed.
UNASSIGNED: We observed that RT, VTP and Cryo significantly delayed tumor growth and extended overall survival. In addition, they also induced regression of non-treated distant tumors in a bilateral model suggesting a systemic immune response. Flow cytometry showed that VTP and Cryo are associated with a reduction in CD11b+ myeloid cells (granulocytes, monocytes, and macrophages) in tumor and periphery. An increase in CD8+ T cell infiltration into tumors was observed only in the RT group. VTP and Cryo were associated with an increase in CD4+ and CD8+ cells in the periphery.
UNASSIGNED: These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT.
UNASSIGNED: Here, we compare three different forms of localize tumor destruction therapies: radiation therapy (RT), vascular targeted photodynamic therapy (VTP) and cryoablation (Cryo), which are known to induce immunogenic cell death, with their ability to induce local and systemic immune responses in a mouse 4T1 breast cancer model. The effects of combining RT, VTP, Cryo with anti-PD1 was also assessed.
UNASSIGNED: We observed that RT, VTP and Cryo significantly delayed tumor growth and extended overall survival. In addition, they also induced regression of non-treated distant tumors in a bilateral model suggesting a systemic immune response. Flow cytometry showed that VTP and Cryo are associated with a reduction in CD11b+ myeloid cells (granulocytes, monocytes, and macrophages) in tumor and periphery. An increase in CD8+ T cell infiltration into tumors was observed only in the RT group. VTP and Cryo were associated with an increase in CD4+ and CD8+ cells in the periphery.
UNASSIGNED: These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT.
摘要：
■免疫疗法正在彻底改变多种癌症类型的管理。然而,只有一部分患者对免疫治疗有反应.抗性的一种机制是肿瘤内不存在免疫浸润。具有可诱导免疫原性细胞死亡的局部肿瘤破坏手段的原位疫苗已显示增强肿瘤T细胞浸润并增加免疫检查点阻断的功效。
■这里，我们比较了三种不同形式的局部肿瘤破坏疗法：放射治疗（RT），血管靶向光动力疗法（VTP）和冷冻消融（Cryo），已知会诱导免疫原性细胞死亡，在小鼠4T1乳腺癌模型中具有诱导局部和全身免疫反应的能力。结合RT的效果，VTP,还评估了抗PD1的冷冻。
■我们观察到RT，VTP和Cryo可显着延迟肿瘤生长并延长总生存期。此外,在提示全身免疫反应的双侧模型中,他们还诱导了未治疗的远处肿瘤消退.流式细胞术显示，VTP和Cryo与CD11b髓样细胞的减少有关（粒细胞，单核细胞,和巨噬细胞）在肿瘤和外周。仅在RT组中观察到CD8+T细胞浸润到肿瘤中的增加。VTP和Cryo与外周CD4+和CD8+细胞的增加相关。
■这些数据表明由VTP和Cryo诱导的细胞死亡引起与局部RT不同的类似免疫应答。
■这里，我们比较了三种不同形式的局部肿瘤破坏疗法：放射治疗（RT），血管靶向光动力疗法（VTP）和冷冻消融（Cryo），已知会诱导免疫原性细胞死亡，在小鼠4T1乳腺癌模型中具有诱导局部和全身免疫反应的能力。结合RT的效果，VTP,还评估了抗PD1的冷冻。
■我们观察到RT，VTP和Cryo可显着延迟肿瘤生长并延长总生存期。此外,在提示全身免疫反应的双侧模型中,他们还诱导了未治疗的远处肿瘤消退.流式细胞术显示，VTP和Cryo与CD11b髓样细胞的减少有关（粒细胞，单核细胞,和巨噬细胞）在肿瘤和外周。仅在RT组中观察到CD8+T细胞浸润到肿瘤中的增加。VTP和Cryo与外周CD4+和CD8+细胞的增加相关。
■这些数据表明由VTP和Cryo诱导的细胞死亡引起与局部RT不同的类似免疫应答。
