Cryoablation: physical and molecular basis with putative immunological consequences
Cryoablation: physical and molecular basis with putative immunological consequences
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DOI：
10.1080/02656736.2019.1647355
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发表时间：
2019-11-29
影响因子：
3.1
通讯作者：
Baust, John M.
中科院分区：
文献类型：
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作者：
Baust, John G.;Snyder, Kristi K.;Baust, John M.
冷冻消融（CA）是唯一的单一能量剥夺疗法，影响所有细胞过程。CA不依赖于细胞周期阶段和细胞干性程度。重要的是，CA通常作为非重复（单次）治疗应用，不支持适应性诱变，如许多重复治疗。CA的特征在于启动多种形式的细胞死亡，包括（a）冰相关的物理损伤，（B）启动细胞应激反应（杀伤开关激活）和启动坏死和凋亡，（c）血管停滞，和（d）可能激活消融性免疫应答。CA并非没有限制地涉及在冷冻探针表面（类似于-185 ℃）和冷冻区的远端表面（类似于0 ℃）之间形成的热梯度，需要冷冻边缘延伸超过肿瘤边界（高达类似于1cm）。这种限制通过通常应用的双重冻融循环和冷冻致敏佐剂的使用而部分减轻。本综述将（1）确定冻融过程的级联损伤效应，其物理和分子基础的关系，（2）可能的免疫参与（abscopic效应），（3）探索使用冷冻增敏佐剂限制冷冻超出肿瘤边缘。
Cryoablation (CA) is unique as the singular energy deprivation therapy that impacts all cellular processes. CA is independent of cell cycle stage and degree of cellular stemness. Importantly, CA is typically applied as a non-repetitive (single session) treatment that does not support adaptative mutagenesis as do many repetitive therapies. CA is characterized by the launch of multiple forms of cell death including (a) ice-related physical damage, (b) initiation of cellular stress responses (kill switch activation) and launch of necrosis and apoptosis, (c) vascular stasis, and (d) likely activation of ablative immune responses. CA is not without limitation related to the thermal gradient formed between cryoprobe surface (similar to-185 degrees C) and the distal surface of the freeze zone (similar to 0 degrees C) requiring freeze margin extension beyond the tumor boundary (up to similar to 1 cm). This limitation is mitigated in part by commonly applied dual freeze thaw cycles and the use of freeze sensitizing adjuvants. This review will (1) identify the cascade of damaging effects of the freeze-thaw process, its physical and molecular-based relationships, (2) a likely immunological involvement (abscopic effect), and (3) explore the use of freeze-sensitizing adjuvants necessary to limit freezing beyond the tumor margin.