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酪氨酸激酶抑制剂对非小细胞肺癌患者接种SARS-CoV-2疫苗后免疫反应的影响

Impact of Tyrosine Kinase Inhibitors on the Immune Response to SARS-CoV-2 Vaccination in Patients with Non-Small Cell Lung Cancer.

作者信息

Hernández-Pedro Norma, Arroyo-Hernández Marisol, Barrios-Bernal Pedro, Romero-Nuñez Eunice, Sosa-Hernandez Victor A, Ávila-Ríos Santiago, Maravillas-Montero José Luis, Pérez-Padilla Rogelio, de Miguel-Perez Diego, Rolfo Christian, Arrieta Oscar

机构信息

Laboratorio de Medicina Personalizada, Instituto Nacional de Cancerología, S.S.A., San Fernando 22 Sección XVI, Tlalpan, Mexico City 14080, Mexico.

Thoracic Oncology Unit, Instituto Nacional de Cancerología, S.S.A., San Fernando 22 Sección XVI, Tlalpan, Mexico City 14080, Mexico.

出版信息

Vaccines (Basel). 2023 Oct 19;11(10):1612. doi: 10.3390/vaccines11101612.

Abstract

Immune dysregulation and cancer treatment may affect SARS-CoV-2 vaccination protection. Antibody production by B-cells play a vital role in the control and clearance of the SARS-CoV-2 virus. This study prospectively explores B-cell seroconversion following SARS-CoV-2 immunization in healthy individuals and non-small cell lung cancer (NSCLC) patients undergoing oncological treatment. 92 NSCLC patients and 27 healthy individuals' blood samples were collected after receiving any COVID-19 vaccine. Serum and mononuclear cells were isolated, and a serum surrogate virus neutralization test kit evaluated SARS-CoV-2 antibodies. B-cell subpopulations on mononuclear cells were characterized by flow cytometry. Patients were compared based on vaccination specifications and target mutation oncological treatment. A higher percentage of healthy individuals developed more SARS-CoV-2 neutralizing antibodies than NSCLC patients (63% vs. 54.3%; = 0.03). NSCLC patients receiving chemotherapy (CTX) or tyrosine kinase inhibitors (TKIs) developed antibodies in 45.2% and 53.7%, of cases, respectively, showing an impaired antibody generation. CTX patients exhibited trends towards lower median antibody production than TKIs (1.0, IQR 83 vs. 38.23, IQR 89.22; = 0.069). Patients receiving immunotherapy did not generate antibodies. A sub-analysis revealed that those with ALK mutations exhibited non-significant trends towards higher antibody titers (63.02, IQR 76.58 vs. 21.78, IQR 93.5; = 0.1742) and B-cells quantification (10.80, IQR 7.52 vs. 7.22, IQR 3.32; = 0.1382) against the SARS-CoV-2 spike protein than EGFR patients; nonetheless, these differences were not statistically significant. This study shows that antibodies against SARS-CoV-2 may be impaired in patients with NSCLC secondary to EGFR-targeted TKIs compared to ALK-directed treatment.

摘要

免疫失调和癌症治疗可能会影响新冠病毒疫苗接种的保护效果。B细胞产生抗体在新冠病毒的控制和清除中起着至关重要的作用。本研究前瞻性地探索了健康个体和接受肿瘤治疗的非小细胞肺癌(NSCLC)患者在接种新冠病毒疫苗后的B细胞血清转化情况。在92例NSCLC患者和27名健康个体接种任何新冠疫苗后采集血样。分离血清和单核细胞,使用血清替代病毒中和试验试剂盒评估新冠病毒抗体。通过流式细胞术对单核细胞上的B细胞亚群进行表征。根据疫苗接种规格和靶向突变肿瘤治疗对患者进行比较。与NSCLC患者相比,更高比例的健康个体产生了更多的新冠病毒中和抗体(63%对54.3%;P = 0.03)。接受化疗(CTX)或酪氨酸激酶抑制剂(TKIs)的NSCLC患者产生抗体的病例分别为45.2%和53.7%,显示出抗体产生受损。CTX患者的抗体产生中位数有低于TKIs患者的趋势(1.0,四分位间距83对38.23,四分位间距89.22;P = 0.069)。接受免疫治疗的患者未产生抗体。一项亚分析显示,与表皮生长因子受体(EGFR)患者相比,携带间变性淋巴瘤激酶(ALK)突变的患者针对新冠病毒刺突蛋白的抗体滴度(63.02,四分位间距76.58对21.78,四分位间距93.5;P = 0.1742)和B细胞定量(10.80,四分位间距7.52对7.22,四分位间距3.32;P = 0.1382)呈现出升高的非显著趋势;尽管如此,这些差异无统计学意义。本研究表明,与ALK靶向治疗相比,接受EGFR靶向TKIs治疗的NSCLC患者针对新冠病毒的抗体可能受损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4408/10611320/3d8b02d97ef1/vaccines-11-01612-g001.jpg

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