免疫疗法正在彻底改变多种癌症类型的治疗。然而，只有一小部分患者对免疫疗法有反应。一种耐药机制是肿瘤内缺乏免疫浸润。具有局部肿瘤破坏手段的原位疫苗可以诱导免疫原性细胞死亡，已被证明可以增强肿瘤 T 细胞浸润并提高免疫检查点封锁的功效。在这里，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) 已知可诱导免疫原性细胞死亡，并且能够在小鼠 4T1 乳腺癌模型中诱导局部和全身免疫反应。还评估了 RT、VTP、Cryo 与抗 PD1 组合的效果。我们观察到 RT、VTP 和 Cryo 显着延迟了肿瘤生长并延长了总体生存期。此外，他们还在双侧模型中诱导未治疗的远处肿瘤消退，这表明存在全身免疫反应。流式细胞术显示 VTP 和 Cryo 与肿瘤和外周 CD11b 骨髓细胞（粒细胞、单核细胞和巨噬细胞）的减少有关。仅在 RT 组中观察到 CD8 T 细胞浸润肿瘤的增加。 VTP 和 Cryo 与外周 CD4 和 CD8 细胞的增加相关。这些数据表明，VTP 和 Cryo 诱导的细胞死亡会引发与局部 RT 不同的类似免疫反应。版权所有 © 2024 Budhu, Kim, Yip, La Rosa, Jebiwott、Cai、Holland、Thomas、Preise、Somma、Gordon、Scherz、Wolchok、Erinjeri、Merghoub 和 Coleman。

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.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.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.These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT.Copyright © 2024 Budhu, Kim, Yip, La Rosa, Jebiwott, Cai, Holland, Thomas, Preise, Somma, Gordon, Scherz, Wolchok, Erinjeri, Merghoub and Coleman.