A5024096172- Immunotherapy and Immune Responses
- Ovarian cancer diagnosis and treatment
- Cancer Immunotherapy and Biomarkers
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Endometrial and Cervical Cancer Treatments
- Cervical Cancer and HPV Research
- Bladder and Urothelial Cancer Treatments
- Pregnancy-related medical research
- Urticaria and Related Conditions
- Phagocytosis and Immune Regulation
- Ureteral procedures and complications
- Renal Diseases and Glomerulopathies
- Renal cell carcinoma treatment
- Abdominal Surgery and Complications
- Cancer Risks and Factors
- Cancer survivorship and care
- Endoplasmic Reticulum Stress and Disease
- Cancer Genomics and Diagnostics
- Family Support in Illness
- Uterine Myomas and Treatments
- Cancer Diagnosis and Treatment
- Cancer-related molecular mechanisms research
University Hospital Hradec Králové
2018-2024
Charles University
2018-2024
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...
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...
<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...
<p>NACT-mediated adjuvanticity positively impacts clinically relevant TLS maturation in metastatic HGSOC. <b>A,</b> Representative image of immunofluorescence CD4, CD8, CD20, CD21, CD23, DC-LAMP, and GZMB staining (immunofluorescence panel 1). Scale bars, 10, 100 500 µm. <b>B</b> <b>C,</b> Distribution early (eTLS; <b>B</b>) mature (mTLS; <b>C</b>) across pTME mTME HGSOC tumor samples with/without NACT. Statistical...
<p>NACT-mediated progenitor TCF1<sup>+</sup>PD1<sup>+</sup>CD8<sup>+</sup> T-cell phenotype associates with effector cytotoxic functions within metastatic HGSOC. <b>A–C,</b> Representative dot plot (<b>A</b>) and box (<b>B</b>) showing percentage of TIM-3<sup>+</sup>PD1<sup>+</sup>CD8<sup>+</sup> T cells GZMB<sup>+</sup>CD8<sup>+</sup> native pTME mTME...
<div>AbstractPurpose:<p>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...
<p>Supplemental material, figures and tables</p>
<p>NACT positively increases the ICI-sensitive TCF1<sup>+</sup>PD1<sup>+</sup>CD8<sup>+</sup> T-cell phenotype within metastatic HGSOC. <b>A,</b> Representative image of immunofluorescence CD68, CD8, PD-L1, FoxP3, TCF1, CD57, PanCK, PD1, CD4, CD20, GZMB, and TIM-3 staining (immunofluorescence panel 2). Scale bars, 2 μm, 10 µm, 100 µm. <b>B,</b> Violin plot showing density CD8<sup>+</sup>...
<p>The clinical relevance of combined chemotherapy and immunotherapy in mouse models TMB<sup>Lo</sup> TMB<sup>Hi</sup> ovarian cancer. <b>A</b> <b>B,</b> Bar plots showing single-nucleotide variants positions (SNVs) (<b>A</b>) the somatic mutations prevalence (mutations per megabase) (<b>B</b>) ID8 (<i>n</i> = 3)...
<p>Univariate Cox proportional hazard analyses.</p>
<p>Immunomodulation by NACT in metastatic HGSOC. <b>A,</b> Representative images of CALR immunostaining CALR<sup>Lo</sup> and CALR<sup>Hi</sup> patients. Scale bars, 10 100 µm. <b>B,</b> expression levels determined (<b>C</b>) ER stress signature level [expression DNA damage inducible transcript 3 (DDIT3, best known as CHOP), heat shock protein family A (Hsp70) member 5 (HSPA5, BIP), 90 beta 1 (HSP90B1)] RNA-seq pTME mTME...
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...
The profile of the antitumor immune response is an important factor determining patient clinical outcome. However, influence tissue contexture on composition tumor microenvironments virally induced tumors not clearly understood. Therefore, we analyzed landscape two HPV-associated malignancies: oropharyngeal squamous cell carcinoma (OPSCC) and uterine cervix (CESC). We employed multiplex immunohistochemistry immunofluorescence to evaluate density spatial distribution cells in retrospective...
Karcinom endometria nadále zůstává nejčastější malignitou v gynekologii rozvinutých zemích. Prevalence roste s věkem a zároveň výskyt onemocnění je častější mezi obézními ženami. Jedná se o relativně nízkou mortalitou, protože převážně bývá zachyceno časném stadiu, kdy omezeno pouze na dělohu. Chirurgická léčba hraje klíčovou roli léčbě jeho raných, lokalizovaných stadiích. V posledních letech zaznamenáváme odklon od tradičních metod operačního přístupu z otevřené laparotomie ve prospěch...
Navzdory klesající incidenci a účinné prevenci představuje karcinom hrdla dělohy v České republice nadále veliký společenský medicínský problém. Ročně se naší zemi diagnostikuje více než 700 případů zhoubného onemocnění dělohy, přičemž asi 300 pacientek ročně tomuto podlehne. Mezioborová spolupráce, zkušenosti jednotlivých aplikujících odborníků (lékařů, sester, medicínských fyziků asistentů atd.), moderní přístrojové vybavení i dostupnost inovativních léků mají obrovský dopad na stále...
Chirurgická léčba zhoubných novotvarů hrdla děložního prodělala za poslední dekády mnoho změn. Přes jednoduché operace a následnou radikalitu léčby až po postupnou přeměnu k personalizované medicíně. V článku se snažíme retrospektivně zhodnotit vývoj chirurgické od počátků chirurgie současnost.
Karcinom vaječníku je heterogenní onemocnění s celkově špatnou prognózou, jehož léčba by měla být nastavena ohledem na kvalitu života a přežití pacientky. Základem správného nastavení léčebné strategie kvalitní předoperační diagnostika mezioborová spolupráce. V časném stadiu představuje chirurgická primárně léčebný stagingový účel v pokročilém léčebnou modalitou se snahou dosáhnout optimální resekce. Chirurgická koncentrována do onkogynekologických center zkušenostmi danou problematikou. U...
Supplementary Figure from An Autologous Dendritic Cell Vaccine Promotes Anticancer Immunity in Patients with Ovarian Cancer Low Mutational Burden and Cold Tumors