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首页> 美国卫生研究院文献>other >Exploring the Concept of Radiation Booster Shot in Combination with an Anti-PD-L1 mAb to Enhance Anti-Tumor Immune Effects in Mouse Pancreas Tumors
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Exploring the Concept of Radiation Booster Shot in Combination with an Anti-PD-L1 mAb to Enhance Anti-Tumor Immune Effects in Mouse Pancreas Tumors

机译：探索与 PD-L1单抗结合使用以增强小鼠胰腺肿瘤的抗肿瘤免疫效应的辐射助推器概念

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Radiotherapy (RT) has long been known to be immunogenic. Mounting preclinical data demonstrate a synergistic anti-tumor effect when RT is used in combination with immune check point inhibitors (ICI). However, it is unclear how to best integrate RT with an ICI (i.e. dose fractionation, sequence, etc.). Here we explored the concept that RT delivered as an in situ tumor vaccine sequentially to separate tumors over time might stimulate more potent and rapid antitumor immune response than RT delivered to only one tumor. In essence, radiation to a second tumor could be likened to giving a vaccine “booster shot”. Mice bearing pancreatic tumors in three different sites were injected with anti-PD-L1 antibody and exposed to three daily consecutive fractions of 4 Gy each at one or two sites with a one week interval. Our data indicate that delivering an RT to one tumor followed by an RT “booster shot” to a second tumor, compared to treating only one tumor with RT, significantly reduced tumor growth at a third non-irradiated site. This abscopal effect to the non-irradiated site was observed earlier (day 9) in mice that received RT to two tumors versusa single tumor (day 17). Decreased growth of the non-irradiated tumor correlated with a transient increase of the CD4/CD8 ratio in the tumor, increase myeloid-derived suppressor cells and tumor associated macrophages in the draining lymph nodes. These data warrant further exploration of sequentially treating multiple lesions with RT and ICI with the intent of generating a robust anti-tumor immune response.
机译：长期以来，放射疗法（RT）具有免疫原性。越来越多的临床前数据表明，将RT与免疫检查点抑制剂（ICI）组合使用时，具有协同抗肿瘤作用。但是，尚不清楚如何将RT与ICI最佳整合（即剂量分级，序列等）。在这里，我们探讨了一个概念，即RT作为随地随地依次转移的原位肿瘤疫苗，随着时间的推移可能会比仅递送给一个肿瘤的RT刺激更有效，更快速的抗肿瘤免疫应答。从本质上讲，对第二种肿瘤的辐射可以比作疫苗的“助推器”。在三个不同部位的胰腺肿瘤小鼠中注射抗PD-L1抗体，并在一个或两个部位以三个星期的间隔连续暴露于3个每日连续的4 Gy每日级分中。我们的数据表明，与仅用RT治疗一个肿瘤相比，将RT传递给一个肿瘤，然后将RT“助推器”传递给第二个肿瘤，显着降低了第三个非照射部位的肿瘤生长。较早（第9天）在接受RT治疗两个肿瘤的小鼠中观察到了对非照射部位的这种绝对效应（相对于单个肿瘤，第17天）。未辐射肿瘤的生长减少与肿瘤中CD4 / CD8比值的瞬时增加相关，增加了髓样来源的抑制细胞和引流淋巴结中与肿瘤相关的巨噬细胞。这些数据保证了进一步探索，以产生强大的抗肿瘤免疫应答为目的，依次用RT和ICI治疗多个病变。

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