Page content

News from the lab

Welcome to the Laboratory of Cancer Biology and Immunotherapy at Charles University Faculty of Medicine. Under the leadership of Dr. Monika Holubová, Ph.D., our laboratory has established itself as a center for single cell analysis and cancer immunotherapy research.

Our research

Cancer is one of the most common causes of death in the world. Over the past decades, cancer research has yielded new drugs such as specific molecular inhibitors and immunotherapies that positively impact patient outcomes. However, despite these great advances, many patients still die as a direct result of cancer, and new biomarkers and therapies are still being sought to improve survival.

The Cancer Biology and Immunotherapy Laboratory studies cancer (particularly hematological malignancies) to identify potential biomarkers to improve disease detection, prediction and prognosis, and to identify processes and interactions that could help develop or improve immunotherapies for these diseases.

We are currently focusing on:

  • Development and testing of immunotherapies especially for hematological malignancies (cell therapy including CAR)
  • Tumor microenvironment with focus on immune cells and mesenchymal stem cells
  • Analysis of individual tumor cells and immune cells in hematological malignancies
  • Liquid biopsies with focus on cell-free RNA in plasma
  • Heterogeneity of tumor cells

International activities

Dr. Holubová is the founder and leader of the Consortium for iNKT Cell Research and Therapy (CiRT), an international coalition of researchers focused on the development of iNKT cell-based technologies. The Consortium brings together clinicians and scientists from around the world with three main goals:

  • Accelerating the translation of basic iNKT immunobiology research into clinical practice
  • Raising awareness of iNKT developments and successes
  • Building a strong community of advocates for iNKT cell-based therapies

This international network focuses on the development of novel cell and gene therapies to improve outcomes in the areas of:

  • Cancer treatment
  • Organ and bone marrow transplantation
  • Infectious diseases
  • Autoimmune diseases

International Cooperation

  • Dr. Valentina Caputo – Fakulta aplikovaných věd, London South Bank University, Velká Británie
  • doc. Iros Barozzi – Institut pro výzkum rakoviny, Lékařská univerzita Vídeň, Rakousko
  • doc. Aleksander Jankowski – Institut informatiky, Varšavská univerzita, Polsko
  • Dr. Christian Schmidl – LIT – Leibnizův institut pro imunoterapii, Univerzitní nemocnice Regensburg, Německo

Home cooperation

  • Hematologicko-onkologické oddělení, Fakultní nemocnice Plzeň
  • Nové technologie pro informační společnost (NTIS), Západočeská univerzita v Plzni
  • Český národní registr dárců dřeně, Plzeň
  • I. interní klinika, Fakultní nemocnice Plzeň
  • SOTIO a.s., Praha

Education

Our laboratory actively participates in international scientific education, co-organizing the prestigious Summer School of Single Cell Analysis in collaboration with the NTIS Research Centre. This biennial event brings together scientists and researchers from around the world and establishes Pilsen as a recognised centre for single cell analysis research.

Our team

  • Mgr. Monika Holubová, Ph.D. – head of laboratory (immunotherapy, flow cytometry)
    holubovam@fnplzen.cz, 377 104 645
  • MUDr. Miroslava Čedíková, Ph.D. – post-doc. (supervisor of pre-graduate students, immunotherapy)
    miroslava.cedikova@lfp.cuni.cz, 377 593 320
  • Mgr. Pavel Ostašov, Ph.D. – senior researcher (sequencing, liquid biopsies)
    pavel.ostasov@lfp.cuni.cz, 377 593 845
  • Assoc. professor Antonia Rotolo – consultant (supervisor for immunotherapy) Antonia.Rotolo@pennmedicine.upenn.edu
  • Mgr. Jana Skálová – laboratory assistant (laboratory management, cell culture)
    jana.skalova2@lfp.cuni.cz, 377 593 842
  • Adéla Makrlíková, DiS. – laboratory technician
    adela.makrlikova@lfp.cuni.cz
PhD students
  • MUDr. Tereza Dekojová: „I study NK cells and iNKTs in multiple myeloma. I characterize these cells by broad immunophenotyping in patients, monitor them after treatment and compare them with healthy donors. I also evaluate the autologous graft composition and its role in autologous transplantation outcome.“
  • MUDr. Lenka Hejretová: „I focus on cellular immunotherapy of GvHD after allogeneic hematopoietic stem cell transplantation. I am looking for the most effective application and manufacturing protocols of MSC in GVHD treatment. Specifically, I focused on comparing immunomodulatory potential between pooled and single donor MSCs product.Further, I investigate invariant NKT lymphocytes, their reconstitution after aloHSCT and their potential for the production of autologous cell products.“
  • MUDr. Tomáš Kříž: „Mým hlavním zaměřením je studium iNKT buněk v rámci jejich imunorekonstituce po trasplantaci hematopoetických kmenových buněk u pacientů s hematologickými malignitami a jejich potenciál v prevenci/léčbě nemoci štěpu proti hostiteli. Obecněji mě velmi zajímá role iNKT buněk u hematologických malignit a jejich potenciál v rámci imunoterapie těchto chorob.“
  • Mgr. Robin Klieber: „I focus on the research of free circulating long RNAs from the plasma of patients with non-Hodgkin’s lymphomas using next-generation sequencing. The aim is to find new markers for the monitoring of tumor behaviour. I am also interested in single-cell transcriptomics and extracellular vesicles from plasma and conditioned culture media.“
  • Mgr. Diana Macečková: „My research is concerned with epigenetic changes in acute myeloid leukemia, with special focus to alternative splicing. My work is to monitor changes of splice variants during treatment and to evaluate their potential role in chemoresitance using shRNA. The aim is to improve the knowledge about the mechanisms of chemoresistance and to detect new possible targets for specific treatment.“
  • Mgr. Eliška Jandová: „Můj výzkum se specializuje na regulaci genové exprese imunoterapeutických cílů u hematologických malignit. Hlavním záměrem je popsat, jak je exprese u vybraných terapeutických cílů regulovaná a následně otestovat molekuly, které by expresi těchto cílů mohly ovlinit tak, aby cíle, které jsou inhibovány vlivem tlaku terapie, byly znovu exprimovány.“

External members
  • doc. RNDr. Martin Pešta, Ph.D.
  • Ing. et Ing. Jiří Polívka, Ph.D.

Publications

Publications 2023
  • Holicek P, Truxova I, Rakova J, Salek C, Hensler M, Kovar M, Reinis M, Mikyskova R, Pasulka J, Vosahlikova S, Remesova H, Valentova I, Lysak D, Holubova M, Kaspar P, Prochazka J, Kasikova L, Spisek R, Galluzzi L, Fucikova J. Type I interferon signaling in malignant blasts contributes to treatment efficacy in AML patients. Cell Death Dis. 2023 Mar 24;14(3):209. IF 9.696 https://doi.org/10.1038/s41419-023-05728-w
  • PRAJKA, Lukáš – ČEDÍKOVÁ, Miroslava – PROCHÁZKOVÁ, Anežka – KABÍČKOVÁ, Kateřina – MIKLOVIČOVÁ, Gabriela – GRUNDMANOVÁ, Martina – KUNOVÁ, Magdalena – HUMPLÍK, Jan – BOUDA, Jiří. Subpopulace lymfocytů u pacientek s ovariálním endometriomem a zdravých žen – pilotní studie. Aktuální gynekologie a porodnictví. 2023, 2023(15), 9-15. ISSN 1803-9588.
  • Peterkova K, Vorel J, Ilgova J, Ostasov P, Fajtova P, Konecny L, Chanova M, Kasny M, Horn M, Dvorak J. Proteases and their inhibitors involved in Schistosoma mansoni egg-host interaction revealed by comparative transcriptomics with Fasciola hepatica eggs. Int J Parasitol. 2023 Feb 6:S0020-7519(23)00032-2. https://doi.org/10.1016/j.ijpara.2022.12.007

Publications 2022
  • Hejretová Lenka; Weberová Karolína; Čedíková Miroslava; Lysák Daniel; Jindra Pavel; Holubová Monika. Invariantní NKT buňky a jejich využití pro imunomodulaci GvHD – souhrn literatury a preklinická data. Transfuze a hematologie dnes, 28(3), 164-172.
  • Narayan S, Courcoubetis G, Mason J, Naghdloo A, Kolenčík D, Patterson SD, Kuhn P, Shishido SN. Defining A Liquid Biopsy Profile of Circulating Tumor Cells and Oncosomes in Metastatic Colorectal Cancer for Clinical Utility. Cancers (Basel). 2022 Oct 6;14(19):4891. IF 6.575 https://doi.org/10.3390/cancers14194891
  • Holý P, Hlaváč V, Ostašov P, Brynychová V, Koževnikovová R, Trnková M, Kopečková K, Měšťáková S, Mrhalová M, Souček P. Germline and somatic genetic variability of oxysterol-related genes in breast cancer patients with early disease of the luminal subtype. Biochimie. 2022 Aug;199:158-169. IF 4.372 https://doi.org/10.1016/j.biochi.2022.04.015
  • Kolenčík D, Narayan S, Thiele JA, McKinley D, Gerdtsson AS, Welter L, Hošek P, Ostašov P, Vyčítal O, Brůha J, Fiala O, Šorejs O, Liška V, Pitule P, Kuhn P, Shishido SN. Circulating Tumor Cell Kinetics and Morphology from the Liquid Biopsy Predict Disease Progression in Patients with Metastatic Colorectal Cancer Following Resection. Cancers (Basel). 2022 Jan 27;14(3):642. IF 6.575 https://doi.org/10.3390/cancers14030642

Publications 2021
  • KŘÍŽKOVÁ, Věra – ŠIGUTOVÁ, Pavla – HOLUBOVÁ, Monika – ŠTAMBACHOVÁ, Alena – DOLEJŠOVÁ, Martina – LYSÁK, Daniel – DVOŘÁK, Pavel – VLAS, Tomáš – BUFKA, Jiří – VAŇKOVÁ, Lenka – HRUBÁ, Karolína – NGUYEN, Thu Huyen – MARŠÁLOVÁ, Lucie – BOUŘ, Petr. Blood and Blood Components, Hematopoiesis, Selected Methods Used in Cytology, Histology and Hematology. 1st ed. Prague: Karolinum, 2021. Učební texty Univerzity Karlovy. 89 s. ISBN 978-80-246-4709-8.
  • Pandey S, Tuma Z, Smrhova T, Cedikova M, Macanova T, Chottova Dvorakova M. Laser Capture Microdissection Coupled Capillary Immunoassay to Study the Expression of PCK-2 on Spatially-Resolved Islets of Rat Langerhans. Pharmaceutics. 2021 Jun 15;13(6):883. IF 6.29 https://doi.org/10.3390/pharmaceutics13060883
  • Kladnicka I, Cedikova M, Jedlicka J, Kohoutova M, Muller L, Plavinova I, Kripnerova M, Bludovska M, Kuncova J, Mullerova D. Chronic DDE Exposure Modifies Mitochondrial Respiration during Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Mature Adipocytes. Biomolecules. 2021 Jul 21;11(8):1068. IF 5.88 https://doi.org/10.3390/biom11081068
  • Lysák D, Hejretová L, Hrabětová M, Jindra P. Should We Stop Collecting the Preoperative Autologous Blood before Bone Marrow Harvest? J Clin Med. 2021 May 14;10(10):2134. IF 4.964 https://doi.org/10.3390/jcm10102134
  • Machuldova, A., Houdova, L., Kratochvilova, K., Leba, M., Jindra, P., Ostasov, P., Maceckova, D., Klieber, R., Gmucova, H., Sramek, J., & Holubova, M. (2021). Single-Nucleotide Polymorphisms in MICA and MICB Genes Could Play a Role in the Outcome in AML Patients after HSCT. Journal of clinical medicine, 10(20), 4636. IF 4.964 https://doi.org/10.3390/jcm10204636
  • Lysak, D., Brychtová, M., Leba, M., Čedíková, M., Georgiev, D., Jindra, P., Vlas, T., & Holubova, M. (2021). Long-Term Cryopreservation Does Not Affect Quality of Peripheral Blood Stem Cell Grafts: A Comparative Study of Native, Short-Term and Long-Term Cryopreserved Haematopoietic Stem Cells. Cell transplantation, 30, 9636897211036004. IF 4.139 https://doi.org/10.1177/09636897211036004
  • Machuldova A, Holubova M, Caputo VS, Cedikova M, Jindra P, Houdova L and Pitule P (2021) Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation. Front. Immunol. 12:651751. IF 7.97 https://doi.org/10.3389/fimmu.2021.651751
  • Fiala, O., Ostašov, P., Rozsypalová, A., Hora, M., Šorejs, O., Šustr, J., Bendová, B., Trávníček, I., Filipovský, J., Fínek, J., & Büchler, T. (2021). Metformin Use and the Outcome of Metastatic Renal Cell Carcinoma Treated with Sunitinib or Pazopanib. Cancer management and research, 13, 4077–4086. IF 3.46 https://doi.org/10.2147/CMAR.S305321
  • Fiala O, Ostašov P, Rozsypalová A, Hora M, Šorejs O, Šustr J, Bendová B, Trávníček I, Filipovský J, Fínek J, Büchler T. Impact of Concomitant Cardiovascular Medication on Survival of Metastatic Renal Cell Carcinoma Patients Treated with Sunitinib or Pazopanib in the First Line. Target Oncol.2021 Sep;16(5):643-652. IF 4.864 https://doi.org/10.1007/s11523-021-00829-y
  • Navvabi, N., Kolikova, P., Hosek, P., Zitricky, F., Navvabi, A., Vycital, O., Bruha, J., Palek, R., Rosendorf, J., Liska, V., & Pitule, P. (2021). Altered Expression of MBNL Family of Alternative Splicing Factors in Colorectal Cancer. Cancer genomics & proteomics, 18(3), 295–306. IF 3.48 https://doi.org/10.21873/cgp.20260
  • Hlaváč, V., Václavíková, R., Brynychová, V., Ostašov P., Koževnikovová, R., Kopečková, K., Vrána, D., Gatěk, J., & Souček, P. (2021). Role of Genetic Variation in Cytochromes P450 in Breast Cancer Prognosis and Therapy Response. International journal of molecular sciences, 22(6), 2826. IF 6.208 https://doi.org/10.3390/ijms22062826
  • Rakova, J., Truxova, I., Holicek, P., Salek, C., Hensler, M., Kasikova, L., Pasulka, J., Holubova, M., Kovar, M., Lysak, D., Kline, J. P., Racil, Z., Galluzzi, L., Spisek, R., & Fucikova, J. (2021). TIM-3 levels correlate with enhanced NK cell cytotoxicity and improved clinical outcome in AML patients. Oncoimmunology, 10(1), 1889822. IF 7.723 https://doi.org/10.1080/2162402X.2021.1889822
  • Ulrychová, L., Ostašov, P., Chanová, M., Mareš, M., Horn, M., & Dvořák, J. (2021). Spatial expression pattern of serine proteases in the blood fluke Schistosoma mansoni determined by fluorescence RNA in situ hybridization. Parasites & vectors, 14(1), 274. IF 4.047 https://doi.org/10.1186/s13071-021-04773-8

Equipment and methods

Equipment:

  • NGS (MiSeq, NextSeq)
  • Sanger Sequencing (3500 Genetic Analyzer)
  • qPCR (LightCycler 96 System, CFX96 Touch Real-Time PCR Detection System)
  • Flow Cytometry (BD FACSAria Fusion)
  • Microscopy (Olympus IX83 with Yokogawa CSU W1 Confocal Head)
  • Live-Cell Imaging (Incucyte Live-Cell Analysis System)
  • Microarrays (SureScan Microarray Scanner)

Methods:

  • Processing of biological samples (cryopreservation of MNC, RNA/DNA isolation, serum/plasma collection)
  • Expression analysis (qPCR and mass spectrometry)
  • Cloning and gene manipulation
  • Sequencing – Sanger, NGS
  • Immunophenotyping – flow cytometry, immunohistochemistry
  • Cultivation of cell lines and primary cells