Sci Rep:细胞外HMGB1在膀胱癌辐射抵抗性异位模型中的免疫调控作用

2019-05-04 AlexYang MedSci原创

根治性膀胱切除术(RC)与双边盆腔淋巴结清扫术是肌肉侵入性膀胱癌(MIBC)的标准治疗方法。然而,基于辐射的治疗方法,比如三联理疗法(TMT)包括了经尿道膀胱肿瘤切除术(TURBT)、放射疗法(XRT)和化疗增敏剂,代表了一种具有吸引力的、入侵更少的选择。尽管如此,25%-30%的MIBC患者在TMT治疗后会出现局部复发,并且一半的患者会发展为转移。肿瘤细胞的辐射抵抗性是治疗后局部复发的一种潜在起

根治性膀胱切除术(RC)与双边盆腔淋巴结清扫术是肌肉侵入性膀胱癌(MIBC)的标准治疗方法。然而,基于辐射的治疗方法,比如三联理疗法(TMT)包括了经尿道膀胱肿瘤切除术(TURBT)、放射疗法(XRT)和化疗增敏剂,代表了一种具有吸引力的、入侵更少的选择。尽管如此,25%-30%的MIBC患者在TMT治疗后会出现局部复发,并且一半的患者会发展为转移。肿瘤细胞的辐射抵抗性是治疗后局部复发的一种潜在起因。HMGB1在膀胱癌辐射抵抗中具有作用,具体是通过在细胞内促进DNA损伤修复和自噬来实现的。

最近,有研究人员发现,HMGB1在被辐射的肿瘤细胞中被动释放。然而,细胞外HMGB1在影响辐射响应方面的角色和在XRT后调控肿瘤免疫微环境中的精准角色仍旧所知甚少。研究人员鉴定了HMGB1免疫学功能在膀胱癌辐射抵抗性中的新机制。辐射和细胞外HMGB1抑制组合使用能够显著的改善肿瘤的辐射响应并导致免疫的显著变化。更多的是,辐射组合HMGB1抑制能够显著的削弱肿瘤MDSCs和TAMs浸润,不包括Tregs,并且能够将总的肿瘤免疫平衡向抗肿瘤响应方向转变。

最后,研究人员指出,细胞外HMGB1通过促进促肿瘤免疫机制来参与膀胱癌的辐射抵抗性。

原始出处:

Mina Ayoub, Surashri Shinde-Jadhav, Jose Joao Mansure et al. The immune mediated role of extracellular HMGB1 in a heterotopic model of bladder cancer radioresistance. Sci Rep. 23 Apr 2019

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    2019-05-22 yige2012
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    2019-05-06 jiyangfei
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    2019-05-04 留走人康

    膀胱癌真怪,明明是免疫敏感性肿瘤,为什么PD-1治疗效果不好呢?难道靶点不对?将来CD47会不会有效

    0

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    2019-05-04 CHANGE

    梅斯里提供了很多疾病的模型计算公式,赞一个!

    0

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