International Research Center, Translational Immuno-oncology Group, A.C.Camargo Cancer Center, São Paulo, Brazil.
Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Front Immunol. 2023 Jan 9;13:1052104. doi: 10.3389/fimmu.2022.1052104. eCollection 2022.
The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted health across all sectors of society. A cytokine-release syndrome, combined with an inefficient response of innate immune cells to directly combat the virus, characterizes the severe form of COVID-19. While immune factors involved in the development of severe COVID-19 in the general population are becoming clearer, identification of the immune mechanisms behind severe disease in oncologic patients remains uncertain.
Here we evaluated the systemic immune response through the analysis of soluble blood immune factors and anti-SARS-CoV-2 antibodies within the early days of a positive SARS-CoV-2 diagnostic in oncologic patients.
Individuals with hematologic malignancies that went on to die from COVID-19 displayed at diagnosis severe leukopenia, low antibody production against SARS-CoV-2 proteins, and elevated production of innate immune cell recruitment and activation factors. These patients also displayed correlation networks in which IL-2, IL-13, TNF-alpha, IFN-gamma, and FGF2 were the focal points. Hematologic cancer patients that showed highly networked and coordinated anti-SARS-CoV-2 antibody production, with central importance of IL-4, IL-5, IL-12A, IL-15, and IL-17A, presented only mild COVID-19. Conversely, solid tumor patients that had elevated levels of inflammatory cytokines IL-6, CXCL8, and lost the coordinate production of anti-virus antibodies developed severe COVID-19 and died. Patients that displayed positive correlation networks between anti-virus antibodies, and a regulatory axis involving IL-10 and inflammatory cytokines recovered from the disease. We also provided evidence that CXCL8 is a strong predictor of death for oncologic patients and could be an indicator of poor prognosis within days of the positive diagnostic of SARS-CoV-2 infection.
Our findings defined distinct systemic immune profiles associated with COVID-19 clinical outcome of patients with cancer and COVID-19. These systemic immune networks shed light on potential immune mechanisms involved in disease outcome, as well as identify potential clinically useful biomarkers.
由冠状病毒 SARS-CoV-2 引起的 COVID-19 大流行影响了社会各阶层的健康。细胞因子释放综合征，加上先天免疫细胞对直接对抗病毒的低效反应，是 COVID-19 严重形式的特征。虽然越来越清楚地了解了普通人群中 COVID-19 严重程度相关的免疫因素，但确定肿瘤患者严重疾病背后的免疫机制仍不确定。
在这里，我们通过分析肿瘤患者 SARS-CoV-2 诊断阳性早期的可溶性血液免疫因子和抗 SARS-CoV-2 抗体来评估系统免疫反应。
因 COVID-19 而死亡的血液恶性肿瘤患者在诊断时表现出严重的白细胞减少症、对 SARS-CoV-2 蛋白产生低抗体、以及先天免疫细胞募集和激活因子的产生增加。这些患者还显示出相互关联的网络，其中 IL-2、IL-13、TNF-alpha、IFN-gamma 和 FGF2 是焦点。表现出高度网络化和协调的抗 SARS-CoV-2 抗体产生、IL-4、IL-5、IL-12A、IL-15 和 IL-17A 具有中心重要性的血液恶性肿瘤患者仅表现出轻度 COVID-19。相反，具有升高水平的炎症细胞因子 IL-6、CXCL8 并失去抗病毒抗体协调产生的实体瘤患者发展为严重 COVID-19 并死亡。表现出抗病毒抗体之间呈正相关网络以及涉及 IL-10 和炎症细胞因子的调节轴的患者从疾病中恢复。我们还提供了证据表明 CXCL8 是肿瘤患者死亡的强有力预测因子，并可能在 SARS-CoV-2 感染阳性诊断后的几天内成为预后不良的指标。
我们的发现定义了与癌症和 COVID-19 患者 COVID-19 临床结局相关的独特系统免疫特征。这些系统免疫网络揭示了疾病结局中涉及的潜在免疫机制，并确定了潜在的临床有用生物标志物。
