Harnessing cancer immunotherapy during the unexploited immediate perioperative period
Harnessing cancer immunotherapy during the unexploited immediate perioperative period
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DOI：
10.1038/s41571-019-0319-9
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发表时间：
2020-02-17
影响因子：
78.8
通讯作者：
Ben-Eliyahu, Shamgar
中科院分区：
文献类型：
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作者：
Matzner, Pini;Sandbank, Elad;Ben-Eliyahu, Shamgar
手术仍然是癌症治疗的关键支柱，特别是对于那些可治愈的、局部的疾病。围手术期（手术前后几天）与各种心理和生理压力及相关因素（包括炎症介质）有关，这些因素可能促进癌症进展，从而决定长期预后。在此，作者提出了假设和支持证据，即使用某些类型的免疫疗法，以及消除应激炎症反应的干预措施，结合手术可能会提高癌症治疗的总体成功率。围手术期（手术前后几天）被认为是决定癌症长期预后的关键因素：在这段短时间内，许多因素，包括过度应激和炎症反应、肿瘤细胞脱落、促血管生成和/或生长因子，可能促进原有微转移的进展和新转移的开始，同时损害对残留恶性细胞的免疫控制。因此，在这一关键时期应用抗癌免疫疗法可能会潜在地改善患者的预后。然而，这一战略迄今很少得到执行。在这一观点中，我们讨论了围手术期使用癌症免疫治疗的明显禁忌症，建议在这一重要时间框架内安全的免疫治疗和其他抗转移方法，并指定这些干预措施的期望特征。这些特征包括免疫激活的快速开始，避免肿瘤促进作用，手术风险没有或只有很小的增加，对压力相关因素的适应能力和最小的应激反应诱导。药物控制过度围手术期应激炎症反应已被证明是临床可行的，并可能与免疫刺激相结合，以克服手术的直接促转移效应，防止免疫抑制并增强免疫刺激反应。因此，我们认为，某些类型的免疫治疗，连同消除应激炎症反应的干预措施，应该与手术一起进行评估，为了获得最大的效果，可以在给予辅助治疗之前开始。这样的策略可能会提高癌症治疗的总体成功率。
Surgery remains a key pillar of cancer therapy, particular for those with curable, localized disease. The immediate perioperative period (days before and after surgery) is associated with various psychological and physiological stresses and associated factors, including inflammatory mediators, that might promote cancer progression and thus determine long-term outcomes. Herein, the authors present the hypothesis and supporting evidence that the use of certain types of immunotherapy, together with interventions to abrogate stress-inflammatory responses, in conjunction with surgery might improve the overall success of cancer treatment.The immediate perioperative period (days before and after surgery) is hypothesized to be crucial in determining long-term cancer outcomes: during this short period, numerous factors, including excess stress and inflammatory responses, tumour-cell shedding and pro-angiogenic and/or growth factors, might facilitate the progression of pre-existing micrometastases and the initiation of new metastases, while simultaneously jeopardizing immune control over residual malignant cells. Thus, application of anticancer immunotherapy during this critical time frame could potentially improve patient outcomes. Nevertheless, this strategy has rarely been implemented to date. In this Perspective, we discuss apparent contraindications for the perioperative use of cancer immunotherapy, suggest safe immunotherapeutic and other anti-metastatic approaches during this important time frame and specify desired characteristics of such interventions. These characteristics include a rapid onset of immune activation, avoidance of tumour-promoting effects, no or minimal increase in surgical risk, resilience to stress-related factors and minimal induction of stress responses. Pharmacological control of excess perioperative stress-inflammatory responses has been shown to be clinically feasible and could potentially be combined with immune stimulation to overcome the direct pro-metastatic effects of surgery, prevent immune suppression and enhance immunostimulatory responses. Accordingly, we believe that certain types of immunotherapy, together with interventions to abrogate stress-inflammatory responses, should be evaluated in conjunction with surgery and, for maximal effectiveness, could be initiated before administration of adjuvant therapies. Such strategies might improve the overall success of cancer treatment.