School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Institute of Immunology, Third Military Medical University, Chongqing 400038, China.
Vaccine. 2023 Jul 31;41(34):4986-4995. doi: 10.1016/j.vaccine.2023.06.053. Epub 2023 Jun 20.
The COVID-19 vaccinations are crucial in protecting against the global pandemic. However, accumulating studies revealed the severely blunted COVID-19 vaccine effectiveness in cancer patients. The PD-1/PD-L1 immune checkpoint blockade (ICB) therapy leads to durable therapeutic responses in a subset of cancer patients and has been approved to treat a wide spectrum of cancers in the clinic. In this regard, it is pivotal to explore the potential impact of PD-1/PD-L1 ICB therapy on COVID-19 vaccine effectiveness during ongoing malignancy. In this study, using preclinical models, we found that the tumor-suppressed COVID-19 vaccine responses are largely reverted in the setting of PD-1/PD-L1 ICB therapy. We also identified that the PD-1/PD-L1 blockade-directed restoration of COVID-19 vaccine effectiveness is irrelevant to anti-tumor therapeutic outcomes. Mechanistically, the restored COVID-19 vaccine effectiveness is entwined with the PD-1/PD-L1 blockade-driven preponderance of follicular helper T cell and germinal center responses during ongoing malignancy. Thus, our findings indicate that PD-1/PD-L1 blockade will greatly normalize the responses of cancer patients to COVID-19 vaccination, while regardless of its anti-tumor efficacies on these patients.
COVID-19 疫苗在预防全球大流行方面至关重要。然而，越来越多的研究表明，癌症患者 COVID-19 疫苗的有效性严重降低。PD-1/PD-L1 免疫检查点阻断（ICB）疗法在一部分癌症患者中能带来持久的治疗反应，并已在临床上获准用于治疗广泛的癌症。在这方面，探索 PD-1/PD-L1 ICB 疗法对正在进行的恶性肿瘤中 COVID-19 疫苗有效性的潜在影响至关重要。在这项研究中，我们使用临床前模型发现，在 PD-1/PD-L1 ICB 治疗的情况下，肿瘤抑制的 COVID-19 疫苗反应在很大程度上被逆转了。我们还发现，PD-1/PD-L1 阻断介导的 COVID-19 疫苗有效性的恢复与抗肿瘤治疗效果无关。从机制上讲，恢复的 COVID-19 疫苗有效性与 PD-1/PD-L1 阻断驱动的滤泡辅助 T 细胞和生发中心反应的优势有关，而这些反应正在进行中恶性肿瘤。因此，我们的研究结果表明，PD-1/PD-L1 阻断将极大地规范癌症患者对 COVID-19 疫苗接种的反应，而不管其对这些患者的抗肿瘤疗效如何。
