UOSD Clinical Trial Center, Biostatistics and Bioinformatics, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy.
Cell Death Dis. 2021 Oct 29;12(11):1019. doi: 10.1038/s41419-021-04299-y.
Clinical outcomes of COVID-19 patients are worsened by the presence of co-morbidities, especially cancer leading to elevated mortality rates. SARS-CoV-2 infection is known to alter immune system homeostasis. Whether cancer patients developing COVID-19 present alterations of immune functions which might contribute to worse outcomes have so far been poorly investigated. We conducted a multi-omic analysis of immunological parameters in peripheral blood mononuclear cells (PBMCs) of COVID-19 patients with and without cancer. Healthy donors and SARS-CoV-2-negative cancer patients were also included as controls. At the infection peak, cytokine multiplex analysis of blood samples, cytometry by time of flight (CyTOF) cell population analyses, and Nanostring gene expression using Pancancer array on PBMCs were performed. We found that eight pro-inflammatory factors (IL-6, IL-8, IL-13, IL-1ra, MIP-1a, IP-10) out of 27 analyzed serum cytokines were modulated in COVID-19 patients irrespective of cancer status. Diverse subpopulations of T lymphocytes such as CD8T, CD4T central memory, Mucosal-associated invariant T (MAIT), natural killer (NK), and γδ T cells were reduced, while B plasmablasts were expanded in COVID-19 cancer patients. Our findings illustrate a repertoire of aberrant alterations of gene expression in circulating immune cells of COVID-19 cancer patients. A 19-gene expression signature of PBMCs is able to discriminate COVID-19 patients with and without solid cancers. Gene set enrichment analysis highlights an increased gene expression linked to Interferon α, γ, α/β response and signaling which paired with aberrant cell cycle regulation in cancer patients. Ten out of the 19 genes, validated in a real-world consecutive cohort, were specific of COVID-19 cancer patients independently from different cancer types and stages of the diseases, and useful to stratify patients in a COVID-19 disease severity-manner. We also unveil a transcriptional network involving gene regulators of both inflammation response and proliferation in PBMCs of COVID-19 cancer patients.
COVID-19 患者的临床结果因合并症而恶化，尤其是癌症导致死亡率升高。已知 SARS-CoV-2 感染会改变免疫系统的稳态。目前，关于患有 COVID-19 的癌症患者是否存在可能导致更差结局的免疫功能改变知之甚少。我们对 COVID-19 患者和无癌症患者的外周血单核细胞（PBMC）中的免疫参数进行了多组学分析。还纳入了健康供体和 SARS-CoV-2 阴性癌症患者作为对照。在感染高峰期，对血液样本进行细胞因子多重分析、飞行时间（CyTOF）细胞群体分析以及使用 PBMC 上的 PanCancer 阵列进行 Nanostring 基因表达分析。我们发现，在 COVID-19 患者中，无论癌症状态如何，27 种分析的血清细胞因子中有 8 种促炎因子（IL-6、IL-8、IL-13、IL-1ra、MIP-1a、IP-10）发生了调节。CD8T、CD4T 中央记忆、黏膜相关不变 T（MAIT）、自然杀伤（NK）和γδ T 细胞等多种 T 淋巴细胞亚群减少，而 COVID-19 癌症患者中的 B 浆母细胞则扩增。我们的研究结果说明了 COVID-19 癌症患者循环免疫细胞中存在一系列异常的基因表达改变。PBMC 的 19 个基因表达特征能够区分 COVID-19 患者和无实体癌患者。基因集富集分析突出了与干扰素α、γ、α/β 反应和信号相关的基因表达增加，这与癌症患者的异常细胞周期调节相关。在一个真实世界的连续队列中验证的 10 个基因，独立于不同的癌症类型和疾病阶段，是 COVID-19 癌症患者特有的，可用于 COVID-19 疾病严重程度的分层。我们还揭示了 COVID-19 癌症患者 PBMC 中涉及炎症反应和增殖基因调节剂的转录网络。
