A5090378329- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Ovarian cancer diagnosis and treatment
- Cancer Mechanisms and Therapy
- Immune Cell Function and Interaction
- Adipose Tissue and Metabolism
- Immune cells in cancer
- CAR-T cell therapy research
- Fatty Acid Research and Health
- Acute Myeloid Leukemia Research
- Adipokines, Inflammation, and Metabolic Diseases
- Cancer Cells and Metastasis
- Regulation of Appetite and Obesity
- Diet and metabolism studies
- PARP inhibition in cancer therapy
- Peroxisome Proliferator-Activated Receptors
- Cancer, Stress, Anesthesia, and Immune Response
- Metabolism, Diabetes, and Cancer
- interferon and immune responses
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Cell death mechanisms and regulation
- Liver Disease Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Bladder and Urothelial Cancer Treatments
Sotio (Czechia)
2015-2024
Czech Academy of Sciences
2006-2020
Czech Academy of Sciences, Institute of Physiology
2008-2020
Florida College
2001
University of Florida
2001
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...
Abstract Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients cancer, reflecting their contribution to the development tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates varying degrees organization and maturation. Specifically, mature TLSs (mTLS) as forming only 16% HGSOCs relatively elevated tumor mutational burden (TMB) are an increased...
Caspase 3 (CASP3) has a key role in the execution of apoptosis, and many cancer cells are believed to disable CASP3 as mechanism resistance cytotoxic therapeutics. Alongside, regulates stress-responsive immunomodulatory pathways, including secretion type I interferon (IFN). Here, we report that mouse mammary carcinoma TSA lacking Casp3 or subjected chemical caspase inhibition were sensitive cytostatic effects radiation therapy (RT) vitro their control counterparts, yet secreted increased...
Abstract Hormone receptor (HR) + breast cancer (BC) causes most BC-related deaths, calling for improved therapeutic approaches. Despite expectations, immune checkpoint blockers (ICBs) are poorly active in patients with HR BC, part reflecting the lack of preclinical models that recapitulate disease progression immunocompetent hosts. We demonstrate mammary tumors driven by medroxyprogesterone acetate (M) and 7,12-dimethylbenz[a]anthracene (D) several key features human luminal B HER2 −...
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...
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...
The successful implementation of immune checkpoint inhibitors (ICI) in the clinical management various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due immunologic features including limited tumor mutational burden (TMB) and poor lymphocytic infiltration. An autologous dendritic cell (DC)-based vaccine (DCVAC) recently been shown be safe significantly improve progression-free survival (PFS) a...
<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...
OBJECTIVE The induction of obesity, dyslipidemia, and insulin resistance by high-fat diet in rodents can be prevented n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). We tested a hypothesis whether AMP-activated protein kinase (AMPK) has role the beneficial effects LC-PUFAs. RESEARCH DESIGN AND METHODS Mice with whole-body deletion α2 catalytic subunit AMPK (AMPKα2−/−) their wild-type littermates were fed on either low-fat chow, or corn oil-based (cHF), cHF 15% lipids replaced LC-PUFA...
The obesogenic effect of a high-fat (HF) diet is counterbalanced by stimulation energy expenditure and lipid oxidation in response to meal. aim this study was reveal whether muscle nonshivering thermogenesis could be stimulated HF diet, especially obesity-resistant A/J compared with obesity-prone C57BL/6J (B/6J) mice. Experiments were performed on male mice born maintained at 30°C. Four-week-old randomly weaned onto low-fat (LF) or for 2 wk. In the LF mice, cold exposure (4°C) resulted...
Insulin resistance, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation availability, i.e., metabolic inflexibility. This, turn, contributes further damage of insulin signaling. Effectiveness T2D treatment depends large part on improvement sensitivity and adaptability muscle, main site whole-body glucose utilization. We have shown previously mice fed an obesogenic high-fat diet that combined use n-3 long-chain polyunsaturated fatty acids (n-3...
Antibodies targeting the co-inhibitory receptor programmed cell death 1 (PDCD1, best known as PD-1) or its main ligand CD274 (best PD-L1) have shown some activity in patients with metastatic triple-negative breast cancer (TNBC), especially a recent Phase III clinical trial combining PD-L1 blockade taxane-based chemotherapy. Despite these encouraging findings, however, most TNBC fail to derive significant benefits from blockade, calling for identification of novel therapeutic approaches....
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...
LTX-315 is a nonameric oncolytic peptide in early clinical development for the treatment of solid malignancies. Preclinical and evidence indicates that anticancer properties originate not only from its ability to selectively kill cancer cells, but also capacity promote tumor-targeting immune responses. Here, we investigated therapeutic activity immunological correlates intratumoral administration three syngeneic mouse models breast carcinoma, with focus on identification possible...
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....
The n‐3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic (DHA), exert hypolipidemic effects prevent development of obesity insulin resistance in animals fed high‐fat diets. We sought to determine the efficacy α‐substituted DHA derivatives as lipid‐lowering, antiobesity, antidiabetic agents. C57BL/6 mice were given a corn oil‐based (35% weight/weight) diet (cHF), or cHF with 1.5% lipids replaced α‐methyl ethyl ester (Substance 1), α‐ethyl 2),...
Abstract Purpose: Patients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of effector cells HGSOC microenvironment stand out promising combinatorial partners for ICIs this oncological...
<p>NACT-mediated adjuvanticity positively impacts the density of follicular T cells (T<sub>FH</sub>) and <i>in situ</i> activation intratumoral B in mHGSOC. <b>A–C,</b> Representative image (<b>A</b>) box plots showing CD4<sup>+</sup> (<b>B</b>) CXCR5<sup>+</sup>PD1<sup>+</sup>FoxP3<sup>−</sup>CD4<sup>+</sup> T<sub>FH</sub> (<b>C</b>) pTME mTME...