Pancreatic ductal adenocarcinoma (PDAC) continues to have a dismal prognosis, in part, due to ineffective treatment strategies. The efficacy of some chemotherapies and especially radiotherapy is mediated partially by the immune system. Therefore, we hypothesized that profiling the immune response following chemotherapy and/or irradiation can be used as a readout for treatment efficacy but also to help identify optimal therapeutic schedules for PDAC. Using murine models of PDAC, we demonstrated that concurrent administration of stereotactic body radiotherapy (SBRT) and a modified dose of FOLFIRINOX (mFX) resulted in superior tumor control when compared with single or sequential treatment groups. Importantly, this combined treatment schedule enhanced the magnitude of immunogenic cell death, which in turn amplified tumor antigen presentation by dendritic cells and intratumoral CD8+ T-cell infiltration. Concurrent therapy also resulted in systemic immunity contributing to the control of established metastases. These findings provide a rationale for pursuing concurrent treatment schedules of SBRT with mFX in PDAC.

中文翻译：

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评估化疗和放疗后免疫原性细胞死亡的程度揭示了治疗胰腺癌的新策略。

胰腺导管腺癌（PDAC）的预后仍然不佳，部分原因是治疗策略无效。一些化疗，尤其是放疗的疗效部分是由免疫系统介导的。因此，我们假设分析化疗和/或放疗后的免疫反应可以作为治疗效果的读数，也可以帮助确定 PDAC 的最佳治疗方案。使用 PDAC 小鼠模型，我们证明，与单一或序贯治疗组相比，立体定向全身放射治疗 (SBRT) 和改良剂量的 FOLFIRINOX (mFX) 的同时给药可实现更好的肿瘤控制。重要的是，这种联合治疗方案增强了免疫原性细胞死亡的程度，进而放大了树突状细胞的肿瘤抗原呈递和瘤内 CD8+ T 细胞浸润。同步治疗还产生了全身免疫，有助于控制已形成的转移。这些发现为在 PDAC 中推行 SBRT 与 mFX 同步治疗方案提供了理论依据。