Department of General Surgery, Brooke Army Medical Center, Fort Sam Houston, TX, USA.
Department of Surgery, Uniformed Services University, Bethesda, MD, USA.
Expert Rev Anticancer Ther. 2021 Jul;21(7):739-746. doi: 10.1080/14737140.2021.1894932. Epub 2021 Mar 9.
: Existing HER2-targeted therapies modulate the tumor microenvironment and the immunologic response cancer in a favorable way. While these therapies have made dramatic improvements in the treatment and prognosis of HER2-overexpressing malignancies, additional treatment options are still needed.: This review covers the immunomodulatory effects of approved HER2-targeted therapies. We discuss the preclinical data that demonstrate an additive effect of the combination of trastuzumab or other HER2-targeting agents with immunomodulatory drugs. Finally, we report the initial studies on the combination of HER2-targeted agents together with immune checkpoint inhibitors or cancer vaccines in breast cancer.: Preclinical data suggest a synergistic effect of HER2-targeted therapy together with both checkpoint inhibitor and cancer vaccine immunotherapy. Results from initial trials with PD-1/PD-L1-blocking therapy together with HER2-targeted therapy have been negative, but responses were seen in patients with PD-L1+ breast cancer. Trastuzumab together with HER2-targeted cancer vaccination has shown benefits in triple negative breast cancer. Further trials are necessary and warranted to confirm the benefit of these combinations.
现有的 HER2 靶向治疗以有利的方式调节肿瘤微环境和癌症的免疫反应。虽然这些治疗方法显著改善了 HER2 过表达恶性肿瘤的治疗和预后，但仍需要额外的治疗选择。
这篇综述涵盖了已批准的 HER2 靶向治疗的免疫调节作用。我们讨论了证明曲妥珠单抗或其他 HER2 靶向药物与免疫调节药物联合具有附加效应的临床前数据。最后，我们报告了关于 HER2 靶向药物联合免疫检查点抑制剂或癌症疫苗在乳腺癌中的初步研究。
临床前数据表明，HER2 靶向治疗与检查点抑制剂和癌症疫苗免疫治疗联合具有协同作用。与 HER2 靶向治疗联合使用 PD-1/PD-L1 阻断治疗的初步试验结果为阴性，但在 PD-L1+乳腺癌患者中观察到了应答。曲妥珠单抗与 HER2 靶向癌症疫苗联合应用在三阴性乳腺癌中显示出益处。需要进一步的试验来证实这些联合治疗的益处。
