Table_1_Immune responses to SARS-CoV-2 in vaccinated patients receiving checkpoint blockade immunotherapy for cancer.docx

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 (ClinicalTrials.gov identifier NCT04715438) and CAPTURE study (ClinicalTrials.gov identifier NCT03226886), are warranted and will provide broader safety and immunological data defining the effect of systemic cancer therapies on COVID-19 immunity.

针对SARS-CoV-2的疫苗接种已成功保护癌症患者免受严重感染，然而，COVID-19疫苗接种所引发的免疫反应与癌症免疫治疗过程中产生的免疫反应之间的相互作用尚未得到全面阐述。免疫检查点阻断（ICB）通过扰乱免疫细胞中的抑制性通路来提高其功能并诱导肿瘤免疫，但常会导致严重的免疫相关不良事件（IRAEs）。鉴于COVID-19疫苗接种与ICB均能增强免疫反应，探究这两种治疗方案联合使用是否会引起免疫系统的协同增强至关重要。具体而言，ICB对已接种疫苗患者抗疫苗免疫的影响尤为重要，因为很大一部分符合免疫治疗条件的新诊断癌症患者可能已经接种了COVID-19疫苗。为此，我们研究了ICB对先前接种COVID-19疫苗的癌症患者SARS-CoV-2刺突蛋白（SP）抗体滴度和T细胞反应的影响。从29名接种疫苗的患者和12名未接种疫苗的对照组患者中收集了血液样本，分别在基线（ICB之前）和两次ICB输注后进行。对SARS-CoV-2-SP IgG抗体滴度和T细胞反应进行了量化。与基线反应相比，接种疫苗的个体在接受免疫治疗后，这些免疫反应并无显著差异（P=0.4583，P=0.4571，分别对应）。我们解读这些结果为证据，表明ICB免疫治疗不会显著增强针对SARS-CoV-2的特异性抗体滴度或T细胞反应。尽管我们的研究缺乏相应的IRAEs发生率数据，但结果提供了体液和细胞免疫学数据，支持近期报告，这些报告记录了在接受ICB的患者中，COVID-19疫苗接种的临床安全性和有效性。需要进一步的纵向前瞻性研究，如VOICE研究（ClinicalTrials.gov标识符NCT04715438）和CAPTURE研究（ClinicalTrials.gov标识符NCT03226886），这些研究将提供更广泛的安全性及免疫学数据，以定义系统性癌症治疗对COVID-19免疫的影响。