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{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,4,29]],"date-time":"2023-04-29T04:32:01Z","timestamp":1682742721131},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>To evaluate the benefits of SARS-CoV-2 vaccination in cancer patients it is relevant to understand the adaptive immune response elicited after vaccination. Patients affected by hematologic malignancies are frequently immune-compromised and show a decreased seroconversion rate compared to other cancer patients or controls. Therefore, vaccine-induced cellular immune responses in these patients might have an important protective role and need a detailed evaluation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Certain T cell subtypes (CD4, CD8, Tfh, \u03b3\u03b4T), including cell functionality as indicated by cytokine secretion (IFN, TNF) and expression of activation markers (CD69, CD154) were assessed <jats:italic>via<\/jats:italic> multi-parameter flow cytometry in hematologic malignancy patients (N=12) and healthy controls (N=12) after a second SARS-CoV-2 vaccine dose. The PBMC of post-vaccination samples were stimulated with a spike-peptide pool (S-Peptides) of SARS-CoV-2, with CD3\/CD28, with a pool of peptides from the cytomegalovirus, Epstein-Barr virus and influenza A virus (CEF-Peptides) or left unstimulated. Furthermore, the concentration of spike-specific antibodies has been analyzed in patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results indicate that hematologic malignancy patients developed a robust cellular immune response to SARS-CoV-2 vaccination comparable to that of healthy controls, and for certain T cell subtypes even higher. The most reactive T cells to SARS-CoV-2 spike peptides belonged to the CD4 and Tfh cell compartment, being median (IQR), 3.39 (1.41-5.92) and 2.12 (0.55-4.14) as a percentage of IFN- and TNF-producing Tfh cells in patients. In this regard, the immunomodulatory treatment of patients before the vaccination period seems important as it was strongly associated with a higher percentage of activated CD4 and Tfh cells. SARS-CoV-2- and CEF-specific T cell responses significantly correlated with each other. Compared to lymphoma patients, myeloma patients had an increased percentage of SARS-CoV-2-specific Tfh cells. T-SNE analysis revealed higher frequencies of \u03b3\u03b4T cells in patients compared to controls, especially in myeloma patients. In general, after vaccination, SARS-CoV-2-specific T cells were also detectable in patients without seroconversion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hematologic malignancy patients are capable of developing a SARS-CoV-2-specific CD4 and Tfh cellular immune response after vaccination, and certain immunomodulatory therapies in the period before vaccination might increase the antigen-specific immune response. A proper response to recall antigens (e.g., CEF-Peptides) reflects immune cellular functionality and might be predictive for generating a newly induced antigen-specific immune response as is expected after SARS-CoV-2 vaccination.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1087996","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T13:55:35Z","timestamp":1682690135000},"update-policy":"http:\/\/dx.doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of post-vaccination SARS-CoV-2 T cell subtypes in patients with different hematologic malignancies and 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