Chiarenza Annalisa, Aluisio Gaia Vertillo, Parrinello Nunziatina Laura, Marino Sara, Corsale Anna Maria, Privitera Grete Francesca, Azgomi MojtabaShekarkar, La Spina Enrico, Cambria Daniela, Curtopelle Angelo, Isola Gaetano, Botta Cirino, Di Raimondo Francesco, Romano Alessandra, Santagati Maria
Divisione Di Ematologia, AOU Policlinico Rodolico San Marco, Catania, Italy.
Department of Biomedical and Biotechnological Sciences (BIOMETEC), Section Microbiology University of Catania, Catania, Italy.
Biomark Res. 2025 Feb 10;13(1):25. doi: 10.1186/s40364-025-00734-w.
BACKGROUND: In both chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) immunotherapy determines B-depletion that leads to temporary suppression of humoral immunity, which is clinically relevant especially during the COVID-19 pandemic, when most patients in the first wave received the BNT162b2 vaccine during anti-neoplastic treatment. METHODS: To capture changes in the immunome and microbiome composition in CLL and FL patients upon mRNA-based vaccination, we designed a prospective, longitudinal study to profile both the humoral and the cellular response after exposure to the BNT162b2 COVID-19 vaccine. RESULTS: In both CLL patients and FL patients, the second and third administrations of the BNT162b2 vaccine increased the titer of specific antibodies against SARS-CoV-2. In FL patients, vaccination induced expansion of central memory CD8 + CD57dim CD279 + T cells and reduction of the neutrophil subset myeloid 1 (CD14CD15CD16CD64CD33CD38PDL1HLA-DR); in both cohorts, CD45RA + CD27 + CD279 + NK cells were expanded after a full cycle of vaccination. After vaccination, the genera Collinsella, Gemmiger, Lachnospiraceae, Blautia, Ruminococcus and Lactobacillus increased in both CLL patients and FL patients, whereas Faecalibacterium, Enterobacteriacae, and Enterococcus decreased. Multivariate analysis failed to identify factors associated with changes in microbiome communities among the CLL and FL cohorts, considering age, sex, exposure to anti-CD20 therapy and disease activity. Only in FL patients, alpha diversity was negatively correlated with neutrophil subsets myeloid 1 e 5 at baseline and positively correlated with neutrophil subset 6 after vaccination. PICRUSt2 analysis showed how microbiome can also affect the host health promoting chronic inflammation. The L-lysine biosynthesis pathway was more represented in CLL patients, whereas the L-valine degradation pathway and the anaerobic degradation of purine nucleobases were overrepresented in the FL cohort. CONCLUSIONS: Taken together, our findings reveal the effect of the BNT162b2 vaccine in shaping the microbiome composition in CLL and FL patients, despite receiving treatment for their underlying active disease, and highlight the importance of a comprehensive analysis of the immunome and microbiome profiling to understand immune function in these cohorts of patients.
背景：在慢性淋巴细胞白血病（CLL）和滤泡性淋巴瘤（FL）中，免疫疗法均可导致B细胞耗竭，进而暂时抑制体液免疫，这在临床上具有重要意义，尤其是在新冠疫情期间，第一波疫情中的大多数患者在接受抗肿瘤治疗时接种了BNT162b2疫苗。 方法：为了了解基于mRNA的疫苗接种后CLL和FL患者免疫组和微生物组组成的变化，我们设计了一项前瞻性纵向研究，以分析接触BNT162b2新冠疫苗后的体液和细胞反应。 结果：在CLL患者和FL患者中，第二次和第三次接种BNT162b2疫苗均提高了针对SARS-CoV-2的特异性抗体滴度。在FL患者中，疫苗接种诱导了中央记忆CD8 + CD57dim CD279 + T细胞的扩增，并减少了中性粒细胞亚群髓系1（CD14CD15CD16CD64CD33CD38PDL1HLA-DR）；在两个队列中，经过一个完整的疫苗接种周期后，CD45RA + CD27 + CD279 + NK细胞均有所扩增。接种疫苗后，CLL患者和FL患者体内的柯林斯菌属、Gemmilliger菌属、毛螺菌科、布劳特氏菌属、瘤胃球菌属和乳杆菌属均增加，而粪杆菌属、肠杆菌科和肠球菌属则减少。多因素分析未能确定CLL和FL队列中与微生物群落变化相关的因素，这些因素包括年龄、性别、抗CD20治疗暴露情况和疾病活动度。仅在FL患者中，α多样性在基线时与中性粒细胞亚群髓系1和5呈负相关，在接种疫苗后与中性粒细胞亚群6呈正相关。PICRUSt2分析表明微生物组也可如何影响促进慢性炎症的宿主健康。L-赖氨酸生物合成途径在CLL患者中更为常见，而L-缬氨酸降解途径和嘌呤碱基的厌氧降解途径在FL队列中更为常见。 结论：综上所述，我们的研究结果揭示了BNT162b2疫苗在塑造CLL和FL患者微生物组组成方面的作用，尽管这些患者正在接受潜在活动性疾病的治疗，并强调了全面分析免疫组和微生物组图谱对于了解这些患者队列免疫功能的重要性。
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