CEINGE-Biotecnologie avanzate, scarl, Naples, Italy.
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
Front Immunol. 2023 Aug 29;14:1233056. doi: 10.3389/fimmu.2023.1233056. eCollection 2023.
Thymic epithelial tumors (TETs) are rare malignancies with heterogeneous clinical manifestations. The high frequency of autoimmune paraneoplastic disorders observed in such patients requires caution when using COVID-19 vaccines. Furthermore, TETs are often associated with severe immunodeficiency, making it difficult to predict vaccine immunization. Therefore, we aimed to evaluate immune response to COVID-19 vaccine in patients with TETs.
We conducted a prospective study enrolling patients who underwent the SARS-Cov-2 mRNA full vaccine cycle (two doses plus a booster after 6 months of BNT162b2). All patients were enrolled before receiving 1 vaccine dose and were followed over the vaccination cycle for up to 6 months after the booster dose to i) assess humoral and cellular responses, ii) define biomarkers predictive of effective immunization, and iii) evaluate the safety of the vaccine.
At the end of the full vaccine cycle, 27 (61.4%) patients developed humoral and 38 (86.4%) cellular responses (IFN γ release by stimulated cells) and showed an increase in activated TH1 and TH17 cells, particularly significant after the booster dose. The number of B and T lymphocytes at baseline was predictive of humoral and cellular responses, respectively. Patients with no evidence of tumor lesions had a higher probability of achieving a humoral response than those with evidence of the disease. Furthermore, the percentage of patients with immune-related disorders (75%), particularly Good's syndrome (47.7%) and myasthenia gravis (29.5%), did not change over the entire vaccine cycle. Overall, 19 of the 44 enrolled patients (43.2%) had COVID-19 during the observation period; none required hospitalization or oxygen support, and no fatalities were observed.
SARS-Cov-2 mRNA vaccine determines the immune responses in patients with TET, particularly after the booster dose, and in patients with no evidence of tumor lesions. Preliminary analysis of B and T lymphocytes may help identify patients who have a lower probability of achieving effective humoral and cellular responses and thus may need passive immunization. The vaccine prevented severe COVID-19 infection and is safe.
胸腺瘤（TET）是一种罕见的恶性肿瘤，临床表现具有异质性。此类患者常发生高频自身免疫性副肿瘤疾病，因此在使用 COVID-19 疫苗时需谨慎。此外，TET 常伴有严重的免疫缺陷，难以预测疫苗免疫接种效果。因此，我们旨在评估 TET 患者对 COVID-19 疫苗的免疫反应。
我们进行了一项前瞻性研究，纳入了接受 SARS-CoV-2 mRNA 全疫苗接种周期（两剂加 BNT162b2 后 6 个月加强针）的患者。所有患者在接受第一剂疫苗前入组，并在接种周期内随访至加强针后 6 个月，以评估体液和细胞反应、确定预测有效免疫接种的生物标志物，并评估疫苗的安全性。
在全疫苗接种周期结束时，27 例（61.4%）患者产生了体液反应，38 例（86.4%）患者产生了细胞反应（刺激细胞后 IFNγ释放），并显示出 TH1 和 TH17 激活细胞的增加，尤其是在加强针后更为显著。基线时 B 和 T 淋巴细胞的数量分别预测了体液和细胞反应。无肿瘤病变证据的患者比有疾病证据的患者更有可能产生体液反应。此外，免疫相关疾病患者的比例（75%），特别是 Good 综合征（47.7%）和重症肌无力（29.5%），在整个疫苗接种周期内并未发生变化。在观察期间，44 例入组患者中有 19 例（43.2%）发生了 COVID-19；无患者需要住院或吸氧支持，也未观察到死亡病例。
SARS-CoV-2 mRNA 疫苗在 TET 患者中引起免疫反应，特别是在加强针后，且在无肿瘤病变证据的患者中更明显。初步分析 B 和 T 淋巴细胞可能有助于识别体液和细胞反应有效性较低的患者，从而可能需要被动免疫。疫苗预防了严重的 COVID-19 感染，且安全。
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