@article{MTMT:34829278, title = {Comparative single-cell multiplex immunophenotyping of therapy-naive patients with rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus shed light on disease-specific composition of the peripheral immune system}, url = {https://m2.mtmt.hu/api/publication/34829278}, author = {Balog, József Ágoston and Zvara, Ágnes and Bukovinszki, Vivien and Puskás, László and Balog, Attila and Szebeni, Gábor}, doi = {10.3389/fimmu.2024.1376933}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {15}, unique-id = {34829278}, issn = {1664-3224}, year = {2024}, eissn = {1664-3224}, orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:34486293, title = {Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC.}, url = {https://m2.mtmt.hu/api/publication/34486293}, author = {Gémes, Nikolett and Balog, József Ágoston and Neuperger, Patricia and Schlegl, Erzsébet and Barta, Imre and Fillinger, János and Antus, Balázs and Zvara, Ágnes and Hegedűs, Zoltán and Czimmerer, Zsolt and Manczinger, Máté and Balogh, Gergő Mihály and Tóvári, József and Puskás, László and Szebeni, Gábor}, doi = {10.3389/fimmu.2023.1297577}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34486293}, issn = {1664-3224}, abstract = {Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).Smoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4-/CD8-, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA-/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA-/CD45RO+/CD197-) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups.Our focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients.The applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC.}, keywords = {Tobacco smoking; non-small cell lung cancer; single-cell mass cytometry; CD4 central memory T cells; CD4 effector memory T cells; exacerbating COPD; stable COPD}, year = {2023}, eissn = {1664-3224}, orcid-numbers = {Manczinger, Máté/0000-0003-0831-9617; Tóvári, József/0000-0002-5543-3204; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:34199166, title = {Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy}, url = {https://m2.mtmt.hu/api/publication/34199166}, author = {Neuperger, Patricia and Szalontai, Klára Margit and Gémes, Nikolett and Balog, József Ágoston and Tiszlavicz, László and Furák, József and Lázár, György ifj and Puskás, László and Szebeni, Gábor}, doi = {10.3389/fimmu.2023.1243233}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34199166}, issn = {1664-3224}, year = {2023}, eissn = {1664-3224}, orcid-numbers = {Tiszlavicz, László/0000-0003-1134-6587; Furák, József/0000-0002-7224-1642; Lázár, György ifj/0000-0001-7155-2978; Szebeni, Gábor/0000-0002-6998-5632} } @mastersthesis{MTMT:34108405, title = {Terápia naiv autoimmun betegek perifériás immunrendszerének multiplex jellemzése [Multiplex characterization of the peripheral immune system of therapy naive autoimmune patients]}, url = {https://m2.mtmt.hu/api/publication/34108405}, author = {Balog, József Ágoston}, doi = {10.14232/phd.11572}, publisher = {Universití of Szeged}, unique-id = {34108405}, year = {2023} } @article{MTMT:34076543, title = {Introduction of an Ultraviolet C-Irradiated 4T1 Murine Breast Cancer Whole-Cell Vaccine Model}, url = {https://m2.mtmt.hu/api/publication/34076543}, author = {Szebeni, Gábor and Alföldi, Róbert and Nagy, Lajos I. and Neuperger, Patricia and Gémes, Nikolett and Balog, József Ágoston and Tiszlavicz, László and Puskás, László}, doi = {10.3390/vaccines11071254}, journal-iso = {VACCINES-BASEL}, journal = {VACCINES (BASEL)}, volume = {11}, unique-id = {34076543}, abstract = {The advent of immunotherapy has revolutionized cancer treatments. However, the application of immune checkpoint inhibitors may entail severe side effects, with the risk of therapeutic resistance. The generation of chimeric antigen receptor (CAR) T-cells or CAR-NK cells requires specialized molecular laboratories, is costly, and is difficult to adapt to the rapidly growing number of cancer patients. To provide a simpler but effective immune therapy, a whole-cell tumor vaccine protocol was established based on ultraviolet C (UCV)-irradiated 4T1 triple-negative breast cancer cells. The apoptosis of tumor cells after UVC irradiation was verified using resazurin and Annexin V/propidium iodide flow cytometric assays. Protective immunity was achieved in immunized BALB/c mice, showing partial remission. Adoptive transfer of splenocytes or plasma from the mice in remission showed a protective effect in the naive BALB/c mice that received a living 4T1 tumor cell injection. 4T1-specific IgG antibodies were recorded in the plasma of the mice following immunization with the whole-cell vaccine. Interleukin-2 (IL-2) and oligonucleotide 2006 (ODN2006) adjuvants were used for the transfer of splenocytes from C57BL/6 mice into cyclophosphamide-treated BALB/c mice, resulting in prolonged survival, reduced tumor growth, and remission in 33% of the cases, without the development of the graft-versus-host disease. Our approach offers a simple, cost-effective whole-cell vaccine protocol that can be administered to immunocompetent healthy organisms. The plasma or the adoptive transfer of HLA-matching immunized donor-derived leukocytes could be used as an immune cell therapy for cancer patients.}, year = {2023}, eissn = {2076-393X}, orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632; Tiszlavicz, László/0000-0003-1134-6587} } @article{MTMT:34069256, title = {Comparison of humoral and cellular immune responses in hematologic diseases following completed vaccination protocol with BBIBP-CorV, or AZD1222, or BNT162b2 vaccines against SARS-CoV-2}, url = {https://m2.mtmt.hu/api/publication/34069256}, author = {Szabó, Enikő and Modok, Szabolcs and Rónaszéki, Benedek and Faragó, Anna and Gémes, Nikolett and Nagy, Lajos I. and Hackler, László and Farkas, Katalin and Neuperger, Patricia and Balog, József Ágoston and Balog, Attila and Puskás, László and Szebeni, Gábor}, doi = {10.3389/fmed.2023.1176168}, journal-iso = {FRONT MED}, journal = {FRONTIERS IN MEDICINE}, volume = {10}, unique-id = {34069256}, year = {2023}, eissn = {2296-858X}, orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:33211172, title = {A cytotoxic survey on 2-amino-1H-imidazol based synthetic marine sponge alkaloid analogues}, url = {https://m2.mtmt.hu/api/publication/33211172}, author = {Gémes, Nikolett and Makra, Zsófia and Neuperger, Patricia and Szabó, Enikő and Balog, József Ágoston and Flink, Lili Borbála and Kari, Beáta and Hackler, László and Puskás, László and Kanizsai, Iván and Szebeni, Gábor}, doi = {10.1002/ddr.22006}, journal-iso = {DRUG DEVELOP RES}, journal = {DRUG DEVELOPMENT RESEARCH}, volume = {83}, unique-id = {33211172}, issn = {0272-4391}, abstract = {Here, we describe the synthesis and biologic activity evaluation of 20 novel synthetic marine sponge alkaloid analogues with 2-amino-1H-imidazol (2-AI) core. Cytotoxicity was tested on murine 4T1 breast cancer, A549 human lung cancer, and HL-60 human myeloid leukemia cells by the resazurin assay. A total of 18 of 20 compounds showed cytotoxic effect on the cancer cell lines with different potential. Viability of healthy human fibroblasts and peripheral blood mononuclear cells upon treatment was less hampered compared to cancer cell lines supporting tumor cell specific cytotoxicity of our compounds. The most cytotoxic compounds resulted the following IC50 values 28: 2.91 µM on HL-60 cells, and 29: 3.1 µM on 4T1 cells. The A549 cells were less sensitive to the treatments with IC50 15 µM for both 28 and 29. Flow cytometry demonstrated the apoptotic effect of the most active seven compounds inducing phosphatidylserine exposure and sub-G1 fragmentation of nuclear DNA. Cell cycle arrest was also observed. Four compounds caused depolarization of the mitochondrial membrane potential as an early event of apoptosis. Two lead compounds inhibited tumor growth in vivo in the 4T1 triple negative breast cancer and A549 human lung adenocarcinoma xenograft models. Novel marine sponge alkaloid analogues are demonstrated as potential anticancer agents for further development.}, keywords = {Mannich; 2-amino-(1H)-imidazole; 4T1 breast cancer; A549 lung cancer; HL-60 myeloid leukemia}, year = {2022}, eissn = {1098-2299}, pages = {1906-1922}, orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:33115577, title = {Comparison of Homologous and Heterologous Booster SARS-CoV-2 Vaccination in Autoimmune Rheumatic and Musculoskeletal Patients}, url = {https://m2.mtmt.hu/api/publication/33115577}, author = {Honfi, Dániel György and Gémes, Nikolett and Szabó, Enikő and Neuperger, Patricia and Balog, József Ágoston and Nagy, Lajos I. and Toldi, Gergely and Puskás, László and Szebeni, Gábor and Balog, Attila}, doi = {10.3390/ijms231911411}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33115577}, issn = {1661-6596}, abstract = {Vaccination against SARS-CoV-2 to prevent COVID-19 is highly recommended for immunocompromised patients with autoimmune rheumatic and musculoskeletal diseases (aiRMDs). Little is known about the effect of booster vaccination or infection followed by previously completed two-dose vaccination in aiRMDs. We determined neutralizing anti-SARS-CoV-2 antibody levels and applied flow cytometric immunophenotyping to quantify the SARS-CoV-2 reactive B- and T-cell mediated immunity in aiRMDs receiving homologous or heterologous boosters or acquired infection following vaccination. Patients receiving a heterologous booster had a higher proportion of IgM+ SARS-CoV-2 S+ CD19+CD27+ peripheral memory B-cells in comparison to those who acquired infection. Biologic therapy decreased the number of S+CD19+; S+CD19+CD27+IgG+; and S+CD19+CD27+IgM+ B-cells. The response rate to a booster event in cellular immunity was the highest in the S-, M-, and N-reactive CD4+CD40L+ T-cell subset. Patients with a disease duration of more than 10 years had higher proportions of CD8+TNF-α+ and CD8+IFN-γ+ T-cells in comparison to patients who were diagnosed less than 10 years ago. We detected neutralizing antibodies, S+ reactive peripheral memory B-cells, and five S-, M-, and N-reactive T-cells subsets in our patient cohort showing the importance of booster events. Biologic therapy and <10 years disease duration may confound anti-SARS-CoV-2 specific immunity in aiRMDs.}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Toldi, Gergely/0000-0003-0178-1243; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:32728646, title = {Humoral and cellular immunogenicity and safety of five different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases in remission or with low disease activity and in healthy controls: a single center study}, url = {https://m2.mtmt.hu/api/publication/32728646}, author = {Szebeni, Gábor and Gémes, Nikolett and Honfi, Dániel György and Szabó, Enikő and Neuperger, Patricia and Balog, József Ágoston and Nagy, LI and Szekanecz, Zoltán and Puskás, László and Toldi, Gergely and Balog, Attila}, doi = {10.3389/fimmu.2022.846248}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {32728646}, issn = {1664-3224}, abstract = {Background: Vaccine-induced immunity is essential for controlling the COVID-19 pandemic. Data on humoral and cellular immunogenicity and safety of different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases (RMDs) are limited. Methods: A single center observational study evaluated the immunogenicity and safety of the two-dose regimen of the BBIBP-CorV inactivated, Gam-COVID-Vac and AZD1222 adenovirus-based, and BNT162b2 and mRNA-1273 mRNA-based vaccines in patients with RMDs (n = 89) compared with healthy controls (n = 74). Neutralizing anti-RBD (receptor binding domain) specific antibodies and SARS-CoV-2 specific T-cell response were measured one and four months after the second vaccine dose in parallel with vaccination efficacy and safety. Results: Disease-specific comparison showed that antibody response at four months was higher in spondylarthropathies compared to rheumatoid arthritis and autoimmune RMDs. Risk factors for reduced immunogenicity included longer disease duration, positive immunoserological profile and anti-CD20 therapy of patients. The rate of positive anti-RBD antibody response for healthy controls versus patients after 4 months post vaccination was 69% vs. 55% for the inactivated viral vaccine BBIBP-CorV, 97% vs. 53% for the pooled data of adenovirus vector-based vaccines Gam-COVID-Vac and AZD1222, or 100% vs. 81% for the pooled data of mRNA vaccines BNT162b2 and mRNA-1273, respectively. Patients who received the Gam-COVID-Vac or mRNA-1273 vaccines had a higher proportion of TNF-alpha producing CD4+ T-cells upon SARS-CoV-2 antigen stimulation compared to the inactivated viral vaccine. Conclusion: All five investigated vaccines were immunogenic in the majority of patients and healthy controls with variable antibody and T-cell response and an acceptable safety profile.}, keywords = {Rheumatic and musculoskeletal diseases; CD8(+)T-cell response; SARS-CoV-2 vaccination; anti-RBD neutralizing antibodies; CD4(+) T-cell response}, year = {2022}, eissn = {1664-3224}, orcid-numbers = {Szebeni, Gábor/0000-0002-6998-5632; Toldi, Gergely/0000-0003-0178-1243} } @article{MTMT:32558299, title = {Analysis of the Single-Cell Heterogeneity of Adenocarcinoma Cell Lines and the Investigation of Intratumor Heterogeneity Reveals the Expression of Transmembrane Protein 45A (TMEM45A) in Lung Adenocarcinoma Cancer Patients}, url = {https://m2.mtmt.hu/api/publication/32558299}, author = {Neuperger, Patricia and Balog, József Ágoston and Tiszlavicz, László and Furák, József and Gémes, Nikolett and Kotogány, Edit and Szalontai, Klára Margit and Puskás, László and Szebeni, Gábor}, doi = {10.3390/cancers14010144}, journal-iso = {CANCERS}, journal = {CANCERS}, volume = {14}, unique-id = {32558299}, year = {2022}, eissn = {2072-6694}, orcid-numbers = {Tiszlavicz, László/0000-0003-1134-6587; Furák, József/0000-0002-7224-1642; Szebeni, Gábor/0000-0002-6998-5632} }