Department of Pathology, Xianyang Central Hospital, Xianyang, China.
Department of Pathology, Division of Experimental Diagnostic, KingMed Medical Laboratory (Xi'an) Co., Ltd., Xi'an, China.
Front Immunol. 2023 Aug 3;14:1213222. doi: 10.3389/fimmu.2023.1213222. eCollection 2023.
The utilisation of neoadjuvant immunotherapy has demonstrated promising preliminary clinical outcomes for early-stage resectable non-small-cell lung cancer (NSCLC). Nevertheless, it is imperative to develop novel neoadjuvant combination therapy regimens incorporating immunotherapy to further enhance the proportion of patients who derive benefit. Recent studies have revealed that stereotactic body radiotherapy (SBRT) not only induces direct tumour cell death but also stimulates local and systemic antitumour immune responses. Numerous clinical trials have incorporated SBRT into immunotherapy for advanced NSCLC, revealing that this combination therapy effectively inhibits local tumour growth while simultaneously activating systemic antitumour immune responses. Consequently, the integration of SBRT with neoadjuvant immunotherapy has emerged as a promising strategy for treating resectable NSCLC, as it can enhance the systemic immune response to eradicate micrometastases and recurrent foci post-resection. This review aims to elucidate the potential mechanism of combination of SBRT and immunotherapy followed by surgery and identify optimal clinical treatment strategies. Initially, we delineate the interplay between SBRT and the local tumour immune microenvironment, as well as the systemic antitumour immune response. We subsequently introduce the preclinical foundation and preliminary clinical trials of neoadjuvant SBRT combined with immunotherapy for treating resectable NSCLC. Finally, we discussed the optimal dosage, schedule, and biomarkers for neoadjuvant combination therapy in its clinical application. In conclusion, the elucidation of potential mechanism of neoadjuvant SBRT combined immunotherapy not only offers a theoretical basis for ongoing clinical trials but also contributes to determining the most efficacious therapy scheme for future clinical application.
新辅助免疫治疗在可切除的早期非小细胞肺癌（NSCLC）中显示出有前景的初步临床结果。然而，开发新的包含免疫治疗的新辅助联合治疗方案对于进一步提高受益患者的比例是至关重要的。最近的研究表明，立体定向体部放射治疗（SBRT）不仅诱导直接的肿瘤细胞死亡，而且还刺激局部和全身抗肿瘤免疫反应。许多临床试验已经将 SBRT 纳入晚期 NSCLC 的免疫治疗中，结果表明这种联合治疗有效地抑制了局部肿瘤的生长，同时激活了全身抗肿瘤免疫反应。因此，SBRT 与新辅助免疫治疗的结合成为治疗可切除 NSCLC 的一种很有前途的策略，因为它可以增强全身免疫反应，以消除术后微转移和复发灶。本综述旨在阐明 SBRT 与免疫治疗联合手术的潜在机制，并确定最佳的临床治疗策略。首先，我们描述了 SBRT 与局部肿瘤免疫微环境以及全身抗肿瘤免疫反应之间的相互作用。然后，我们介绍了新辅助 SBRT 联合免疫治疗治疗可切除 NSCLC 的临床前基础和初步临床试验。最后，我们讨论了新辅助联合治疗在临床应用中的最佳剂量、方案和生物标志物。总之，阐明新辅助 SBRT 联合免疫治疗的潜在机制不仅为正在进行的临床试验提供了理论基础，也有助于确定未来临床应用中最有效的治疗方案。
