胸腺上皮肿瘤（TETs）是一种罕见的恶性肿瘤，临床表现多样。这类患者发生自身免疫副肿瘤时的高发率要求在使用COVID-19疫苗时谨慎。此外，TETs通常与严重免疫缺陷相关，这使得预测疫苗免疫效果变得困难。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，招募了接受SARS-Cov-2 mRNA完整疫苗接种（两剂加上BNT162b2 6个月后的加强剂）的患者。所有患者在接受第一剂疫苗之前入组，并在接种周期内进行跟踪观察，持续至加强剂接种后的6个月，以便i)评估体液和细胞反应，ii)确定有效免疫的生物标志物，并iii)评估疫苗的安全性。在完整疫苗接种周期结束时，27（61.4％）例患者表现出体液和38（86.4％）例患者表现出细胞反应（受刺激细胞释放的γ干扰素），并显示出激活的TH1和TH17细胞增加，尤其在加强剂接种后显著。基线时的B和T淋巴细胞数量分别预测了体液和细胞反应。没有肿瘤病灶证据的患者比有病灶证据的患者更有可能产生体液反应。此外，免疫相关紊乱（75％）的患者比例，在整个疫苗接种周期内未发生变化，尤其是仇氏综合征（47.7％）和重症肌无力（29.5％）。总体而言，44例入组患者中，在观察期内有19例（43.2％）患上了COVID-19；没有患者需要住院或氧气支持，并且没有发生死亡病例。SARS-Cov-2 mRNA疫苗决定了TET患者的免疫反应，尤其是在加强剂接种后，以及没有肿瘤病灶证据的患者。对B和T淋巴细胞的初步分析可能有助于确定那些实现有效体液和细胞反应概率较低的患者，因此可能需要被动免疫。该疫苗能够预防严重的COVID-19感染，且安全可靠。版权所有 © 2023 Cernera, Gelzo, De Placido, Ottaviano, Pietroluongo, Raia, Scalia, Tortora, Castaldo, Formisano, Palmieri and Giuliano.

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 1st 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.Copyright © 2023 Cernera, Gelzo, De Placido, Ottaviano, Pietroluongo, Raia, Scalia, Tortora, Castaldo, Formisano, Palmieri and Giuliano.