Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Department of Internal Medicine, University of Toronto, Toronto, ON, Canada.
Cell Death Dis. 2023 Jan 20;14(1):49. doi: 10.1038/s41419-022-05548-4.
Despite more than 2 years having elapsed since the onset of SARS-CoV-2 pandemic, a level of hesitation around increased SARS-CoV-2 vaccine toxicity in cancer patients receiving immunotherapy (IO) remains. This hesitation stems from the idea that IO agents could elicit an overwhelming immune stimulation post vaccination and therefore increase the risk of vaccine-related toxicity. The aim of our study was to explore serological responses to SARS-CoV-2 vaccination in patients treated with IO and describe the level of immune stimulation using parameters such as blood cytokines, autoantibody levels and immune related adverse events (irAEs) post vaccination. Fifty-one evaluable patients were enrolled in this longitudinal study. Absolute levels and neutralization potential of anti-SARS-CoV-2 antibodies were not significantly different in the IO group compared to non-IO. Chemotherapy adversely affected seroconversion when compared to IO and/or targeted treatment. Following vaccination, the prevalence of grade ≥2 irAEs in patients treated with IO was not higher than the usual reported IO toxicity. We report, for the first time, that anti-SARS-CoV-2 vaccination, elicited the generation of five autoantibodies. The significantly increased autoantibodies were IgM autoantibodies against beta-2 glycoprotein (p = 0.02), myeloperoxidase (p = 0.03), nucleosome (p = 0.041), SPLUNC2 (p < 0.001) and IgG autoantibody against Myosin Heavy Chain 6 (MYH6) (p < 0.001). Overall, comprehensive analysis of a small cohort showed that co-administration of SARS-CoV-2 vaccine and IO is not associated with increased irAEs. Nevertheless, the detection of autoantibodies post anti-SARS-CoV-2 vaccination warrants further investigation (NCT03702309).
尽管 SARS-CoV-2 大流行已经过去了 2 年多,但癌症患者在接受免疫治疗(IO)时对 SARS-CoV-2 疫苗毒性增加仍存在一定程度的犹豫。这种犹豫源于这样一种想法,即 IO 药物在接种疫苗后可能会引发过度的免疫刺激,从而增加与疫苗相关的毒性风险。我们的研究旨在探讨接受 IO 治疗的患者对 SARS-CoV-2 疫苗接种的血清学反应,并描述接种疫苗后使用血液细胞因子、自身抗体水平和免疫相关不良事件(irAE)等参数评估的免疫刺激水平。这项纵向研究共纳入了 51 例可评估的患者。与非 IO 组相比,IO 组的抗 SARS-CoV-2 抗体的绝对水平和中和能力没有显著差异。与 IO 和/或靶向治疗相比,化疗会影响血清转化率。接种疫苗后,IO 治疗患者发生≥2 级 irAE 的比例并不高于通常报道的 IO 毒性。我们首次报告抗 SARS-CoV-2 疫苗接种可引发 5 种自身抗体的产生。与 IgG 自身抗体 against Myosin Heavy Chain 6 (MYH6)(p < 0.001)相比,显著增加的自身抗体是针对 beta-2 糖蛋白(p = 0.02)、髓过氧化物酶(p = 0.03)、核小体(p = 0.041)、SPLUNC2(p < 0.001)的 IgM 自身抗体。总的来说,对小队列的综合分析表明,SARS-CoV-2 疫苗和 IO 的联合使用与增加的 irAE 无关。然而,抗 SARS-CoV-2 疫苗接种后自身抗体的检测需要进一步研究(NCT03702309)。