A5026488935- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Acute Myeloid Leukemia Research
- Endoplasmic Reticulum Stress and Disease
- Phagocytosis and Immune Regulation
- Nanoplatforms for cancer theranostics
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Ovarian cancer diagnosis and treatment
- Cancer Research and Treatments
- CAR-T cell therapy research
- Bladder and Urothelial Cancer Treatments
- interferon and immune responses
- Photodynamic Therapy Research Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Melamine detection and toxicity
- Cytokine Signaling Pathways and Interactions
- Cell death mechanisms and regulation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- Immune Response and Inflammation
- Adenosine and Purinergic Signaling
Sotio (Czechia)
2013-2023
Charles University
2014-2020
Karolinska Institutet
2017-2018
University Hospital in Motol
2014
Human papillomavirus (HPV) infection is one of the most important etiologic causes oropharyngeal head and neck squamous cell carcinoma (HNSCC). Patients with HPV-positive HNSCC were reported to have a better clinical outcome than patients HPV-negative cancers. However, little known about possible different outcomes. In this study, we analyzed detailed immune profile tumor samples from respect their HPV status. We characteristics infiltrates, including frequency distribution...
A high density of tumor-infiltrating CD8+ T cells and CD20+ B correlates with prolonged survival in patients a wide variety human cancers, including high-grade serous ovarian carcinoma (HGSC). However, the potential impact mature dendritic (DCs) shaping immune contexture HGSC, their role establishment cell-dependent antitumor immunity, prognostic value for HGSC remain unclear. We harnessed immunohistochemical tests biomolecular analyses to demonstrate that DC-LAMP+ DCs is robustly associated...
Recent studies have identified molecular events characteristic of immunogenic cell death (ICD), including surface exposure calreticulin (CRT), the heat shock proteins HSP70 and HSP90, release high‐mobility group box protein 1 (HMGB1) ATP from dying cells. We investigated potential high hydrostatic pressure (HHP) to induce ICD in human tumor HHP induced rapid expression HSP70, HSP90 CRT on surface. also HMGB1 ATP. The interaction dendritic cells (DCs) with HHP‐treated led a more rate DC...
In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration immune expressing receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic predictive information. Conversely, impact these features microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial.We harnessed a retrospective cohort 80 chemotherapy-naïve HGSC to investigate CD8+ T cells, CD20+ B DC-LAMP+ dendritic well...
Increasing evidence suggests that antibody-drug conjugates (ADCs) can enhance anti-tumor immunity and improve clinical outcome. Here, we elucidate the therapeutic efficacy immune-mediated mechanisms of a novel HER2-targeting ADC bearing potent anthracycline derivate as payload (T-PNU) in human HER2-expressing syngeneic breast cancer model resistant to trastuzumab ado-trastuzumab emtansine. Mechanistically, component induced immunogenic cell death leading exposure secretion danger-associated...
Background The immunological microenvironment of primary high-grade serous carcinomas (HGSCs) has a major impact on disease outcome. Conversely, little is known the metastatic HGSCs and its potential influence patient survival. Here, we explore clinical relevance configuration HGSC metastases. Methods RNA sequencing was employed 24 paired tumor (P-TME) (M-TME) chemotherapy-naive samples. Immunohistochemistry used to evaluate infiltration by CD8 + T cells, CD20 B DC-LAMP (lysosomal-associated...
<h3>Background</h3> Adjuvanticity, which is the ability of neoplastic cells to deliver danger signals, critical for host immune system mount spontaneous and therapy-driven anticancer responses. One such signals<i>,</i> i.e., exposure calreticulin (CALR) on membrane malignant experiencing endoplasmic reticulum (ER) stress, well known its role in activation responses dying cancer cells. However, potential impact CALR contexture primary metastatic high-grade serous carcinomas (HGSCs) prognostic...
Accumulating evidence indicates that immune checkpoint inhibitors (ICIs) can restore CD8+ cytotoxic T lymphocyte (CTL) functions in preclinical models of acute myeloid leukemia (AML). However, ICIs targeting programmed cell death 1 (PDCD1, best known as PD-1) and lymphocyte-associated protein 4 (CTLA4) have limited clinical efficacy patients with AML. Natural killer (NK) cells are central players AML-targeting responses. little is on the relationship between co-inhibitory receptors expressed...
While type I interferon (IFN) is best known for its key role against viral infection, accumulating preclinical and clinical data indicate that robust IFN production in the tumor microenvironment promotes cancer immunosurveillance contributes to efficacy of various antineoplastic agents, notably immunogenic cell death inducers. Here, we report malignant blasts from patients with acute myeloid leukemia (AML) release via a Toll-like receptor 3 (TLR3)-dependent mechanism not driven by treatment....
In some settings, cancer cells responding to treatment undergo an immunogenic form of cell death that is associated with the abundant emission danger signals in damage-associated molecular patterns. Accumulating preclinical and clinical evidence indicates play a crucial role (re-)activation antitumor immune responses vivo, thus having major impact on patient prognosis. We have previously demonstrated presence calreticulin surface malignant blasts positive prognostic biomarker for patients...
Adoptive cell therapy (ACT) is becoming a prominent alternative therapeutic treatment for cancer patients relapsing on traditional therapies. In parallel, antibodies targeting immune checkpoint molecules, such as cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) and death protein 1 pathway (PD-1), are rapidly being approved multiple types, including first line PD-L1-expressing non-small-cell lung cancer. The combination of ACT blockade could substantially boost the efficacy ACT. this...
High hydrostatic pressure (HHP) promotes key characteristics of immunogenic cell death (ICD), in thus far resembling chemotherapy and ionizing irradiation. Here, we demonstrate that cancer cells succumbing to HHP induce CD4+ CD8+ T cell-dependent protective immunity vivo. Moreover, show induction by relies on the overproduction reactive oxygen species (ROS), causing rapid establishment integrated stress response, eIF2α phosphorylation PERK, sequential caspase-2, -8 -3 activation....
High hydrostatic pressure (HHP) has been shown to induce immunogenic cell death of cancer cells, facilitating their uptake by dendritic cells (DC) and subsequent presentation tumor antigens. In the present study, we demonstrated immunogenicity HHP-treated in mice. HHP was able both TC-1 TRAMP-C2 representing murine models for human papilloma virus-associated tumors prostate cancer, respectively. induced stronger immune responses mice immunized with these documented higher spleen cytotoxicity...
Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought establish a protocol generate DC with greater immunostimulatory capacity. Immature were generated from healthy donor monocytes by culturing the presence of IL-4 and GM-CSF further differentiated into mature addition cocktails containing different cytokines toll-like receptor (TLR) agonists....
Dendritic cell (DC)-based vaccines pulsed with high hydrostatic pressure (HHP)-inactivated tumor cells have recently been shown to be a promising tool for prostate cancer chemoimmunotherapy. In this study, DC-based vaccines, both and unpulsed, were as effective docetaxel (DTX) in reducing tumors the orthotopic transgenic adenocarcinoma of mouse (TRAMP) model. However, we did not observe any additive or synergic effects chemoimmunotherapy on growth, while only combination DTX dendritic...
e14008 Background: Immunogenic cell death (ICD) is a form of caused by certain chemicals or physical modalities: cytostatic agents such as anthracyclines, oxaliplatin and bortezomib, radiotherapy photodynamic therapy. Typical molecular events characteristic for ICD are surface exposure calreticulin, HSP70, HSP90, release intranuclear HMGB1 the secretion ATP from dying cells. We investigated potential high hydrostatic pressure (HHP) to induce in human tumor cells analyzed key components...