Research
The cancer immunology group is dedicated to the research of immune cells with a focus on their use for cancer immunotherapy. The first arm of the study investigates immune cells in the tumor microenvironment and the adjacent tissues. The immune cells are first isolated from the tumor and the adjacent tissues, and then their identity and quantity determined. By analyzing specific surface markers on the isolated immune cells, the phenotype of individual populations is characterized. The purpose of the characterization (phenotyping) is to identify immune cell populations whose content in the tumor is associated with a favorable prognosis and which effectively traffic into the tumor.
The second arm of the study is to use the identified immune cell populations for in vitro preparation of cell-based products for adoptive cell immunotherapy of cancer. At this stage, new approaches for specific/selected expansion of the desired cell populations are tested. These approaches consist of prior isolation/enrichment of cell cultures with the desired cell populations. Then these populations are non-specifically expanded using growth factors and/or in vitro-generated dendritic cells. The phenotype of the expanded cells is concomitantly modulated during the expansion phase through pharmacological interventions into selected signaling pathways, such as the Wnt/β-catenin signaling pathway. The expanded cells are next evaluated for their reactivity to tumor cells/antigens and for their ability to eliminate them.
A long-term goal of our research group is an in-depth understanding of the tumor immune microenvironment and the introduction of new technologies for in vitro generation of immune cells for adoptive cell immunotherapy of cancer. In the generated immune cells, we pursue features that would enable their efficient trafficking into the tumors and elimination of the tumor cells, or, at least, enable them to stimulate the immune system in a way that would lead to the elimination of the tumor cells.
People
Principal Investigator
Assoc. prof. Dr. Daniel Smrž, Ph.D.
Senior Scientists/Clinicians
Assoc. prof. Zuzana Ozaniak Střížová, M.D., Ph.D.
Prof. Jiřina Bartůňková, M.D., DrSc.., MBA
Ph.D. Students
Kateřina Kalkušová, MSc. (supervisor: Assoc. prof. Dr. Daniel Smrž, Ph.D.)
Iva Benešová, MSc. (supervisor: Assoc. prof. Zuzana Ozaniak Střížová, M.D., Ph.D.)
Kateřina Kraousová, MSc. (supervisor: Assoc. prof. Dr. Daniel Smrž, Ph.D.)
Students
Miroslava Kolníková (supervisor: Dmitry Stakheev, M.D., Ph.D.)
Matyáš Rázga (supervisor: Pavla Táborská, Ing., Ph. D.)
Lab Technicians
Grants
Current Grants
Ministry of Health of the Czech Republic, project AZV, No. NU23-08-00071, Genetically downregulated expression of the immune checkpoint inhibitor LAIR-1 in tumor-specific T cells as a novel strategy for breaking the resistance of solid tumors to adoptive T cell immunotherapy, 2023–2026
Principle Investigator: Doc. Dr. Daniel Smrž, Ph.D. (Motol University Hospital)
Co-investigator: Luca Vannucci, M.D., Ph.D. (Institute of Microbiology of the CAS)
Ministry of Health of the Czech Republic, project AZV, No. NU22-03-00300, LL-37 as a novel and powerful molecular tool for boosting the performance of ex vivo-produced dendritic cells in immunotherapy of urogenital cancers, 2022–2025
Principle Investigator: Prof. Jiřina Bartůňková, M.D., Ph.D., MBA (Motol University Hospital)
Co-investigator: Doc. Dr. Daniel Smrž, Ph.D. (Charles University, Second Faculty of Medicine)
Past Grants
Technological Agency of the Czech Republic, project TA CR, GAMA 2 (Charles University), No. 202104/TP01010040, A new cell line of undifferentiated pleomorphic sarcoma, 2021–2022
Principle Investigator: Doc. Dr. Daniel Smrž, Ph.D. (Charles University, Second Faculty of Medicine)
The Grant Agency of the Charles University, Czech Republic, No. 364218, Isolation, characterization and expansion of subsets of tumor-infiltrating lymphocytes of kidney cancer for the development of adoptive cell immunotherapy, 2018–2020
Principle Investigator: Zuzana Střížová, M.D., Ph.D. (Charles University, Second Faculty of Medicine)
Supervisor: Doc. Dr. Daniel Smrž, Ph.D. (Charles University, Second Faculty of Medicine)
Charles University, No. PRIMUS/MED/12, Preparation of cytotoxic polyclonal T-cells for adoptive cellular immunotherapy of cancer, 2017–2019
Principle Investigator: Doc. Dr. Daniel Smrž, Ph.D. (Charles University, Second Faculty of Medicine)
Ministry of Health of the Czech Republic, project AZV, No. 16-28135A, Preparation of polyclonal cancer-specific T-cells for adoptive cellular immunotherapy of prostate cancer, 2016–2019
Principle Investigator: Doc. Dr. Daniel Smrž, Ph.D. (Charles University, Second Faculty of Medicine)
Co-investigator: prof. Jiřina Bartůňková, M.D., Ph.D., MBA (Motol University Hospital)
Publications
2024
Rajsiglova, L., M. Babic, K. Krausova, P. Lukac, K. Kalkusova, P. Taborska, L. Sojka, J. Bartunkova, D. Stakheev, L. Vannucci, and D. Smrz. 2024. Immunogenic properties of nickel-doped maghemite nanoparticles and the implication for cancer immunotherapy. Journal of immunotoxicology 21:2416988. DOI: 10.1080/1547691X.2024.2416988
Kalkusova, K., P. Taborska, D. Stakheev, M. Rataj, S. Smite, E. Darras, J. Albo, J. Bartunkova, L. Vannucci, and D. Smrz. 2024. Impaired Proliferation of CD8(+) T Cells Stimulated with Monocyte-Derived Dendritic Cells Previously Matured with Thapsigargin-Stimulated LAD2 Human Mast Cells. Journal of immunology research 2024:5537948. DOI: 10.3390/pharmaceutics14122747
Czech patent (Charles University), Industrial Property Office of the Czech Republic No. 310055 – Cell line and use thereof, invertors: Assoc. Prof. Dr. Daniel Smrž, Ph.D. and Pavla Táborská, Ing., Ph.D. [PCT request for international protection: PCT/CZ2023/050092, WO 2024/132002 A1, Charles University]
Borcinova, M., R. Bartolini, L. K. Foley, V. Novak, P. Taborska, D. Stakheev, M. Rataj, D. Smrz, M. Fialova, J. Hacek, M. Komarc, S. Vesely, M. Babjuk, I. Striz, J. Bartunkova, T. Buchler, and Z. Ozaniak Strizova. 2024. Distinct leukocyte populations and cytokine secretion profiles define tumoral and peritumoral areas in renal cell carcinoma. Translational oncology 42:101891. DOI:10.1016/j.tranon.2024.101891
2023
Taborska, P., P. Lukac, D. Stakheev, L. Rajsiglova, K. Kalkusova, K. Strnadova, L. Lacina, B. Dvorankova, J. Novotny, M. Kolar, M. Vrana, H. Cechova, S. Ransdorfova, M. Valerianova, K. Smetana, Jr., L. Vannucci, and D. Smrz. 2023. Novel PD-L1- and collagen-expressing patient-derived cell line of undifferentiated pleomorphic sarcoma (JBT19) as a model for cancer immunotherapy. Scientific reports 13:19079. DOI: 10.1038/s41598-023-46305-7
2022
Stakheev, D., P. Taborska, K. Kalkusova, J. Bartunkova, and D. Smrz. 2022. LL-37 as a Powerful Molecular Tool for Boosting the Performance of Ex Vivo-Produced Human Dendritic Cells for Cancer Immunotherapy. Pharmaceutics 14. DOI: 10.3390/pharmaceutics14122747
Kalkusova, K., P. Taborska, D. Stakheev, and D. Smrz. 2022. The Role of miR-155 in Antitumor Immunity. Cancers 14. DOI: 10.3390/cancers14215414
Kalkusova, K., S. Smite, E. Darras, P. Taborska, D. Stakheev, L. Vannucci, J. Bartunkova, and D. Smrz. 2022. Mast Cells and Dendritic Cells as Cellular Immune Checkpoints in Immunotherapy of Solid Tumors. International journal of molecular sciences 23. DOI: 10.3390/ijms231911080
Podrazil, M., P. Taborska, D. Stakheev, M. Rataj, J. Lastovicka, A. Vlachova, P. Pohunek, J. Bartunkova, and D. Smrz. 2022. Effectiveness and Durability of mRNA Vaccine-Induced SARS-CoV-2-Specific Humoral and Cellular Immunity in Severe Asthma Patients on Biological Therapy. Frontiers in immunology 13:892277. DOI: 10.3389/fimmu.2022.892277
2021
Bugajev, V., T. Paulenda, P. Utekal, M. Mrkacek, I. Halova, L. Kuchar, O. Kuda, P. Vavrova, B. Schuster, S. Fuentes-Liso, L. Potuckova, D. Smrz, S. Cernohouzova, L. Draberova, M. Bambouskova, and P. Draber. 2021. Crosstalk between ORMDL3, serine palmitoyltransferase, and 5-lipoxygenase in the sphingolipid and eicosanoid metabolic pathways. J Lipid Res:100121. 10.1016/j.jlr.2021.100121
Taborska, P., J. Lastovicka, D. Stakheev, Z. Strizova, J. Bartunkova, and D. Smrz. 2021. SARS-CoV-2 spike glycoprotein-reactive T cells can be readily expanded from COVID-19 vaccinated donors. Immunity, inflammation and disease.10.1002/iid3.496
Bezdicka, M., P. Kleiblova, J. Soucek, M. Borecka, E. El-Lababidi, D. Smrz, M. Rataj, Z. Sumnik, J. Malikova, and O. Soucek. 2021. Novel presentation of the c.1856A > G (p.Asp619Gly) TSHR gene-activating variant: relapsing hyperthyroidism in three subsequent generations manifesting in early childhood and an in vitro functional study. Hormones.10.1007/s42000-021-00299-x
Taborska, P., Z. Strizova, D. Stakheev, L. Sojka, J. Bartunkova, and D. Smrz. 2021. CD4(+) T Cells of Prostate Cancer Patients Have Decreased Immune Responses to Antigens Derived From SARS-CoV-2 Spike Glycoprotein. Frontiers in immunology 12:629102.10.3389/fimmu.2021.629102
Taborska, P., D. Stakheev, J. Bartunkova, and D. Smrz. 2021. Thapsigargin-Stimulated LAD2 Human Mast Cell Line Is a Potent Cellular Adjuvant for the Maturation of Monocyte-Derived Dendritic Cells for Adoptive Cellular Immunotherapy. International journal of molecular sciences 22. 22.10.3390/ijms22083978
Snajdauf, M., K. Havlova, J. Vachtenheim, Jr., A. Ozaniak, R. Lischke, J. Bartunkova, D. Smrz, and Z. Strizova. 2021. The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials. Frontiers in molecular biosciences 8:628332. 10.3389/fmolb.2021.628332
Strizova, Z., M. Kuchar, L. Capkova, M. Komarc, J. Skrivan, J. Bartunkova, J. Plzak, and D. Smrz. 2021. Fas-Fas Ligand Interplay in the Periphery of Salivary Gland Carcinomas as a New Checkpoint Predictor for Disease Severity and Immunotherapy Response. Biomedicines 9. 10.3390/biomedicines9040402
Mucciolo, G., C. Curcio, C. Roux, W. Y. Li, M. Capello, R. Curto, R. Chiarle, D. Giordano, M. A. Satolli, R. Lawlor, A. Scarpa, P. Lukac, D. Stakheev, P. Provero, L. Vannucci, T. W. Mak, F. Novelli, and P. Cappello. 2021. IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions. Proc Natl Acad Sci U S A 118. DOI: 10.1073/pnas.2020395118
Kuchar, M., Z. Strizova, L. Capkova, M. Komarc, J. Skrivan, J. Bartunkova, D. Smrz, and J. Plzak. 2021. The Periphery of Salivary Gland Carcinoma Tumors Reveals a PD-L1/PD-1 Biomarker Niche for the Evaluation of Disease Severity and Tumor-Immune System Interplay. Biomedicines 9. DOI: 10.3390/biomedicines9020097
2020
Taborska, P., D. Stakheev, H. Svobodova, Z. Strizova, J. Bartunkova, and D. Smrz. 2020. Acute Conditioning of Antigen-Expanded CD8(+) T Cells via the GSK3beta-mTORC Axis Differentially Dictates Their Immediate and Distal Responses after Antigen Rechallenge. Cancers 12. 10.3390/cancers12123766
Strizova, Z., D. Smrz, and J. Bartunkova. 2020. Response to Weiss MF re: "Seroprevalence of Borrelia IgM and IgG Antibodies in Healthy Individuals: A Caution Against Serology Misinterpretations and Unnecessary Antibiotic Treatments". Vector Borne Zoonotic Dis. 10.1089/vbz.2020.2690
Strizova, Z., J. Vachtenheim, Jr., M. Snajdauf, R. Lischke, J. Bartunkova, and D. Smrz. 2020. Tumoral and paratumoral NK cells and CD8(+) T cells of esophageal carcinoma patients express high levels of CD47. Scientific reports 10:13936.
Ozaniak, A., Z. Strizova, P. Hladik, and R. Lischke. 2020. Novel therapeutic approaches in the treatment of solitary fibrous tumors: A call for a combination therapy. Cancer 126:4068-4069.
Strizova, Z., J. Bartunkova, and D. Smrz. 2020. Can wearing face masks in public affect transmission route and viral load in COVID-19? Central European journal of public health 28:161-162.
Paces, J., Z. Strizova, D. Smrz, and J. Cerny. 2020. COVID-19 and the immune system. Physiological research. 10.33549/physiolres.934492
Strizova, Z., M. Snajdauf, D. Stakheev, P. Taborska, J. Vachtenheim, Jr., J. Biskup, R. Lischke, J. Bartunkova, and D. Smrz. 2020. The paratumoral immune cell signature reveals the potential for the implementation of immunotherapy in esophageal carcinoma patients. Journal of cancer research and clinical oncology 146:1979-1992.
Strizova, Z., T. Milota, and J. Bartunkova. 2020. COVID-19 from the perspective of an immunologist. Casopis lekaru ceskych 159:67-71.
Strizova, Z., D. Smrz, and J. Bartunkova. 2020. Seroprevalence of Borrelia IgM and IgG Antibodies in Healthy Individuals: A Caution Against Serology Misinterpretations and Unnecessary Antibiotic Treatments. Vector Borne Zoonotic Dis. 10.1089/vbz.2020.2632
2019
Kuchar, M., Z. Strizova, M. Votava, and J. Plzak. 2019. The relevance of Fas/Fas ligand axis in the tumor microenvironment of salivary gland adenoid cystic carcinoma. Oral oncology 97:135-136.
Strizova, Z., J. Vachtenheim, Jr., and J. Bartunkova. 2019. The potential role of neutrophil trogocytosis and G-CSF in the loss of HER2 expression. Breast Cancer Res Treat 178:247-248.
Strizova, Z., J. Bartunkova, and D. Smrz. 2019. The challenges of adoptive cell transfer in the treatment of human renal cell carcinoma. Cancer immunology, immunotherapy : CII 68:1831-1838.
Strizova, Z., P. Taborska, D. Stakheev, S. Partlova, K. Havlova, S. Vesely, J. Bartunkova, and D. Smrz. 2019. NK and T cells with a cytotoxic/migratory phenotype accumulate in peritumoral tissue of patients with clear cell renal carcinoma. Urologic oncology 37:503-509.
Stakheev, D., P. Taborska, Z. Strizova, M. Podrazil, J. Bartunkova, and D. Smrz. 2019. The WNT/beta-catenin signaling inhibitor XAV939 enhances the elimination of LNCaP and PC-3 prostate cancer cells by prostate cancer patient lymphocytes in vitro. Scientific reports 9:4761.
Strizova, Z., O. Patek, L. Vitova, M. Horackova, and J. Bartunkova. 2019. Internet-based self-diagnosis of Lyme disease caused death in a young woman with systemic lupus erythematosus. Joint, bone, spine : revue du rhumatisme 86:650-651.
2018
Taborska, P., J. Bartunkova, and D. Smrz. 2018. Simultaneous in vitro generation of human CD34(+)-derived dendritic cells and mast cells from non-mobilized peripheral blood mononuclear cells. J Immunol Methods 458:63-73.
2017
Taborska, P., D. Stakheev, Z. Strizova, K. Vavrova, M. Podrazil, J. Bartunkova, and D. Smrz. 2017. Personalized ex vivo multiple peptide enrichment and detection of T cells reactive to multiple tumor-associated antigens in prostate cancer patients. Medical oncology 34:173.
