Neuro-Immunology Research Unit, School of Psychological Sciences, Tel-Aviv University, Tel Aviv-Yafo, Israel.
Department of Hematology and Oncology, Kaiser Permanente Northern California, San Francisco, CA, USA.
Nat Rev Clin Oncol. 2020 May;17(5):313-326. doi: 10.1038/s41571-019-0319-9. Epub 2020 Feb 17.
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.
围手术期（手术前后几天）被认为是决定长期癌症结果的关键时期：在这段短暂的时间内，许多因素，包括过度的应激和炎症反应、肿瘤细胞脱落以及促血管生成和/或生长因子，可能会促进先前存在的微转移的进展和新转移的发生，同时危及对残留恶性细胞的免疫控制。因此，在这个关键时期应用抗癌免疫疗法可能会改善患者的预后。然而，迄今为止，这种策略很少被实施。在本观点中，我们讨论了围手术期使用癌症免疫疗法的明显禁忌症，提出了在这一重要时期安全的免疫治疗和其他抗转移方法，并指定了此类干预措施的理想特征。这些特征包括免疫激活的快速起效、避免促进肿瘤生长的作用、不增加或最小化手术风险、对与应激相关的因素有弹性以及最小的应激反应诱导。已经证明，药物控制过度的围手术期应激-炎症反应在临床上是可行的，并且可能与免疫刺激联合使用，以克服手术的直接促转移作用，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疗法，以及消除应激-炎症反应的干预措施，应该与手术一起进行评估，为了达到最大的效果，可以在辅助治疗之前开始。这些策略可能会提高癌症治疗的整体成功率。
