Immune responses to SARS-CoV-2 in vaccinated patients receiving checkpoint blockade immunotherapy for cancer.
Immune responses to SARS-CoV-2 in vaccinated patients receiving checkpoint blockade immunotherapy for cancer.
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DOI：
10.3389/fimmu.2022.1022732
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发表时间：
2022
影响因子：
7.3
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中科院分区：
文献类型：
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针对SARS-CoV-2的疫苗接种成功地保护了癌症患者免受严重感染，但针对COVID-19疫苗接种的免疫应答如何与癌症免疫治疗期间引发的免疫应答相互作用尚未得到充分描述。免疫检查点阻断（ICB）破坏免疫细胞中的抑制途径，以改善功能并诱导肿瘤免疫，但通常会导致严重的免疫相关不良事件（IRAE）。由于COVID-19疫苗接种和ICB都能增强免疫反应，因此必须了解这些方案的结合是否会导致免疫系统的协同增强。具体而言，ICB是否影响先前接种疫苗的患者的抗疫苗免疫力非常重要，因为很大一部分符合免疫治疗条件的新诊断癌症患者已经接种了COVID-19疫苗。为了解决这个问题，我们研究了ICB对先前接种COVID-19疫苗的癌症患者的SARS-CoV-2-刺突蛋白（SP）抗体滴度和T细胞应答的影响。在基线（ICB前）和两轮ICB输注后，从29名接种疫苗的患者和12名未接种疫苗的对照患者中采集人血样。定量抗SARS-CoV-2-SP IgG滴度和T细胞应答。与基线时的应答相比，接种疫苗的个体在免疫治疗后的这些免疫应答没有显著差异（分别为P=0.4583，P=0.4571）。我们将这些结果解释为ICB免疫疗法不会显著增强SARS-CoV-2特异性抗体滴度或T细胞应答的证据。尽管我们的研究缺乏相应的IRAE率，但结果提供了体液和细胞免疫学数据，支持最近记录接受ICB患者接种COVID-19疫苗的临床安全性和有效性的报告。其他纵向前瞻性研究，如VOICE研究（标识符NCT 04715438）和CAPTURE研究（标识符NCT 03226886），将提供更广泛的安全性和免疫学数据，定义全身癌症治疗对COVID-19免疫力的影响。
Vaccination against SARS-CoV-2 has been successful in protecting patients with cancer from severe infections, but how immune responses against COVID-19 vaccination interact with those elicited during cancer immunotherapy has not been fully described. Immune checkpoint blockade (ICB) disrupts inhibitory pathways in immune cells to improve function and induce tumor immunity but can often cause serious immune related adverse events (IRAEs). Because COVID-19 vaccination and ICB both boost immune responses, it is imperative to understand if combining these regimens causes synergistic enhancement of the immune system. Specifically, whether ICB impacts anti-vaccine immunity in previously vaccinated patients is important since a large percentage of newly diagnosed cancer patients eligible for immunotherapy will have already been vaccinated against COVID-19. To address this, we investigated the influence of ICB on SARS-CoV-2-spike protein (SP) antibody titers and T cell responses in cancer patients previously vaccinated against COVID-19. Human blood samples were collected from 29 vaccinated patients and 12 unvaccinated control patients at baseline (prior to ICB) and following two rounds of ICB infusion. Anti-SARS-CoV-2-SP IgG titers and T cell responses were quantified. Compared to responses at baseline, there was no significant difference in these immune responses after immunotherapy in vaccinated individuals (P=0.4583, P=0.4571, respectively). We interpret these results as evidence that ICB immunotherapy does not significantly enhance SARS-CoV-2-specific antibody titers or T cell responses. Although our study lacks corresponding IRAE rates, the results provide humoral and cellular immunological data that support recent reports documenting the clinical safety and efficacy of COVID-19 vaccination in patients receiving ICB. Additional longitudinal prospective studies, such as the VOICE study ( identifier NCT04715438) and CAPTURE study ( identifier NCT03226886), are warranted and will provide broader safety and immunological data defining the effect of systemic cancer therapies on COVID-19 immunity.