抗血管生成治疗联合免疫检查点抑制剂 在NSCLC中的研究进展

血管生成是非小细胞肺癌(NSCLC)生长、复发和转移的关键环节。抗血管生成治疗可以通过使肿瘤血管及微环境正常化,改善肿瘤血供和含氧量,增强放、化疗效果。也可以抑制肿瘤内毛细血管生长,使肿瘤细胞进入休眠状态,并诱导其凋亡。因此,靶向抗血管生成已成为NSCLC治疗研究的主要方向。贝伐珠单抗和雷莫芦单抗已被批准用于联合一线标准化疗治疗局部晚期或转移性NSCLC。然而,在这一治疗过程中,肿瘤会逐渐对抗血管生成药物产生耐药,这可能与肿瘤微环境(tumor microenvironment,TME)的改变有关。最近,免疫检查点抑制剂(immune checkpoint inhibitors,ICI)已经取得了相当大的成功,但是反应率仍然被认为不是最佳的。因此,为了提高疗效,各种组合疗法正在测试中。临床前数据表明促血管生成因子具有免疫抑制作用,为ICI和抗血管生成药物联合使用提供了合理的解释。并且有研究认为,抗血管生成治疗与肿瘤免疫治疗相联合可能是一种相互增益的治疗策略。

Advances in anti-angiogenic therapy combined with immune checkpoint inhibitors in NSCLC

Abstract: Angiogenesis is a key link in the growth, recurrence, and metastasis of non-small cell lung cancer (NSCLC). Anti-angiogenic therapy can improve the blood supply and oxygen content of tumors and enhance the effects of radiotherapy and chemotherapy by normalizing tumor blood vessels and microenvironment. It can also inhibit capillary growth in tumors, put tumor cells into a dormant state, and induce apoptosis. Therefore, anti-angiogenesis therapy has become the main direction of NSCLC treatment research. Bevacizumab and Ramucirumab have been approved for the treatment of local advanced or metastatic NSCLC with first-line standard chemotherapy. However, during this treatment, the tumor will gradually become resistant to anti-angiogenic drugs, which may be related to the changes of the tumor microenvironment (TME). Recently, immune checkpoint inhibitors (ICI) have achieved considerable success, but the response rate is still considered to be not optimal. Therefore, in order to improve the efficacy, various combination therapies are being tested. Preclinical data suggest that pro-angiogenic factors have immunosuppressive effects, providing a reasonable explanation for the combination of ICI and anti-angiogenic drugs. And some studies suggest that anti-angiogenic therapy combined with tumor immunotherapy may be a mutually beneficial treatment strategy.