PURPOSE: Immune checkpoint inhibitors (ICIs) dramatically changed the prognosis of patients with NSCLC. Unfortunately, a reliable predictive biomarker is still missing. Commonly used biomarkers, such as PD-L1, MSI, or TMB, are not quite accurate in predicting ICI efficacy. METHODS: In this prospective observational cohort study, we investigated the predictive role of erythrocytes, thrombocytes, innate and adaptive immune cells, complement proteins (C3, C4), and cytokines from peripheral blood of 224 patients with stage III/IV NSCLC treated with ICI alone (pembrolizumab, nivolumab, and atezolizumab) or in combination (nivolumab + ipilimumab) with chemotherapy. These values were analyzed for associations with the response to the treatment and survival endpoints. RESULTS: Higher baseline Tregs, MPV, hemoglobin, and lower monocyte levels were associated with favorable PFS and OS. Moreover, increased baseline basophils and lower levels of C3 predicted significantly improved PFS. The levels of the baseline immature granulocytes, C3, and monocytes were significantly associated with the occurrence of partial regression at the first restaging. Multiple studied parameters (n = 9) were related to PFS benefit at the time of first restaging as compared to baseline values. In addition, PFS nonbenefit group showed a decrease in lymphocyte count after three months of therapy. The OS benefit was associated with higher levels of lymphocytes, erythrocytes, hemoglobin, MCV, and MPV, and a lower value of NLR after three months of treatment. CONCLUSION: Our work suggests that parameters from peripheral venous blood may be potential biomarkers in NSCLC patients on ICI. The baseline values of Tregs, C3, monocytes, and MPV are especially recommended for further investigation.
- MeSH
- antigeny CD274 MeSH
- biologické markery MeSH
- hemoglobiny terapeutické užití MeSH
- imunofenotypizace MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- lidé MeSH
- nádory plic * MeSH
- nemalobuněčný karcinom plic * MeSH
- nivolumab terapeutické užití MeSH
- prospektivní studie MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: Rituximab (RTX) and ocrelizumab (OCR), B cell-depleting therapy targeting CD20 molecules, affect the humoral immune response after vaccination. How these therapies influence T-cell-mediated immune response against SARS-CoV-2 after immunization remains unclear. We aimed to evaluate the humoral and cellular immune response to the COVID-19 vaccine in a cohort of patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). METHODS: Patients with MS (83), NMOSD (19), or MG (7) undergoing RTX (n=47) or OCR (n=62) treatment were vaccinated twice with the mRNA BNT162b2 vaccine. Antibodies were quantified using the SARS-CoV-2 IgG chemiluminescence immunoassay, targeting the spike protein. SARS-CoV-2-specific T cell responses were quantified by interferon γ release assays (IGRA). The responses were evaluated at two different time points (4-8 weeks and 16-20 weeks following the 2nd dose of the vaccine). Immunocompetent vaccinated individuals (n=41) were included as controls. RESULTS: Almost all immunocompetent controls developed antibodies against the SARS-CoV-2 trimeric spike protein, but only 34.09% of the patients, without a COVID-19 history and undergoing anti-CD20 treatment (via RTX or OCR), seroconverted. This antibody response was higher in patients with intervals of longer than 3 weeks between vaccinations. The duration of therapy was significantly shorter in seroconverted patients (median 24 months), than in the non-seroconverted group. There was no correlation between circulating B cells and the levels of antibodies. Even patients with a low proportion of circulating CD19+ B cells (<1%, 71 patients) had detectable SARS-CoV-2 specific antibody responses. SARS-CoV-2 specific T cell response measured by released interferon γ was detected in 94.39% of the patients, independently of a humoral immune response. CONCLUSION: The majority of MS, MG, and NMOSD patients developed a SARS-CoV-2-specific T cell response. The data suggest that vaccination can induce SARS-CoV-2-specific antibodies in a portion of anti-CD20 treated patients. The seroconversion rate was higher in OCR-treated patients compared to those on RTX. The response represented by levels of antibodies was better in individuals, with intervals of longer than 3 weeks between vaccinations.
- MeSH
- autoimunitní nemoci nervového systému * MeSH
- COVID-19 * MeSH
- glykoprotein S, koronavirus MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- myasthenia gravis * MeSH
- protilátky virové MeSH
- rituximab terapeutické užití MeSH
- roztroušená skleróza * farmakoterapie MeSH
- SARS-CoV-2 MeSH
- vakcína BNT162 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Molecular characterization of tumors could be a key to therapeutic decision-making with regards to targeted therapies in castration-resistant prostate cancer (CRPC). A convenient solution may be non-invasive liquid biopsy testing of circulating tumor cells (CTCs). For this reason, CTC-enriched samples obtained by immunomagnetic separation (AdnaTest®) were studied as a source material for high-throughput gene expression analysis using BioMark™. PATIENTS AND METHODS: CTC-enriched samples from 41 CRPC patients previously determined to be CTC positive using the AdnaTest® were retrospectively re-analysed for androgen receptor (AR) messenger RNA (mRNA), using the updated AdnaTest®. Blood samples were drawn two times from each patient: at the time of CRPC diagnosis and after the third docetaxel cycle. A gene expression panel of 27 genes related to CRPC therapeutic decision-making, including AR full length (ARFL) and splice variant 7 (ARV7), was retrospectively analyzed on a BioMark™ platform in 29 of 41 patients. RESULTS: The AdnaTest® detected AR mRNA in three-quarters of CTC-positive samples taken at the time of CRPC diagnosis and after the third docetaxel cycle. AR detection was associated with a shorter disease-specific survival (45.0 vs. 20.4 months) at the time of CRPC diagnosis. ARFL expression at the time of CRPC diagnosis, measured on the BioMark™ platform, was associated with a lower decrease of serum level of prostate-specific antigen (sPSA) (p = 0.029), i.e., worse therapy response. ARV7 was found in 38% of the ARFL--positive samples at both analyzed timepoints. CONCLUSION: Detection of AR expression by AdnaTest® in CTC-enriched samples may help predict patients' survival. These AdnaTest® CTC-enriched samples can be used in a high-throughput quantitative polymerase chain reaction (qPCR) analysis of gene expression, provided that the specificity of the assay for each individual gene is properly validated. The BioMark™ platform can be used for the simultaneous detection of ARFL and ARV7 and other genes in CTC-enriched samples from CRPC patients.
- MeSH
- genetické testování metody MeSH
- imunomagnetická separace MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * MeSH
- nádorové cirkulující buňky metabolismus patologie MeSH
- nádory prostaty rezistentní na kastraci diagnóza genetika MeSH
- následné studie MeSH
- rychlé screeningové testy MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stanovení celkové genové exprese * metody MeSH
- transkriptom MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND AND AIMS: Metastases are a severe complication in cancer patients and biomarkers predicting their progression are still lacking for specific groups of patients. HER2 positive breast cancer (HER2 BC) patients on trastuzumab therapy are at risk of the development of unpredictable and often fatal central nervous system (CNS) metastases and castration resistant prostate cancer (CRPC) patients urgently need a marker of disease progression during therapy. Proposed metastatic markers: circulating tumor cells (CTC), serum levels of matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and vascular endothelial growth factor (VEGF) were prospectively studied to confirm their utility in these two narrowly defined groups of cancer patients. PATIENTS AND METHODS: The groups comprised 44 advanced HER2 BC, 24 CRPC patients and 42 healthy controls. An immunomagnetic separation method followed by PCR and electrophoretic detection (AdnaGen, Germany) were used for CTC determination. Serum marker levels were determined by the ELISAs (R&D System, USA). RESULTS: MMP-2 serum level was significantly higher in HER2 BC patients who developed CNS metastases, especially if there were also bone metastases. CTCs were a negative predictive marker for overall survival in HER2 BC patients. MMP-9 serum level was significantly higher in CRPC patients in whom disease progression occurred. CTC vanished from the blood of most of the CRPC patients (from 88% to 37%) during chemotherapy. CONCLUSION: MMP-2 serum level and CTCs show the potential to predict CNS metastases and overall survival in BC patients. CTCs and MMP-9 serum level could be a promising therapy response marker in CRPC patients.
- MeSH
- dospělí MeSH
- geny erbB-2 MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 krev MeSH
- matrixová metaloproteinasa 9 krev MeSH
- metastázy nádorů * patologie MeSH
- míra přežití MeSH
- nádorové biomarkery krev MeSH
- nádorové cirkulující buňky patologie MeSH
- nádory centrálního nervového systému krev sekundární MeSH
- nádory prostaty rezistentní na kastraci krev patologie MeSH
- nádory prsu krev metabolismus patologie MeSH
- prediktivní hodnota testů MeSH
- progrese nemoci MeSH
- protinádorové látky imunologicky aktivní aplikace a dávkování MeSH
- trastuzumab aplikace a dávkování terapeutické užití MeSH
- vaskulární endoteliální růstový faktor A krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
1 svazek : ilustrace, tabulky ; 30 cm
The aim of the project is to detect circulating tumor cells (CTC) in peripheral blood of patients with metastatic prostate cancer before and during the cytotoxic therapy. Detection will be performed by the method of immunomagnetic separation and RNA isolation from this fraction. Then we will perform the cultivation of the detected cells including the cultivation in milieu of cytotoxic agents. In the next stage the genetic profile of the detected cells will be assessed (a panel of 24 genes) and a similar profile will be evaluated also in histological specimen of a primary tumor. Analysis results will be correlated to the clinical course of disease and the prognostic factors of treatment effect on CTC count decline and patients‘ survival will be determined.
Cílem projektu je detekovat cirkulující nádorové buňky (CTC) v periferní krvi u pacientů s metastatickým karcinomem prostaty před cytotoxickou léčbou a v jejím průběhu. Detekce bude provedena metodou imunomagnetické separace buněk a izolací RNA z této frakce. Dále proběhne kultivace části detekovaných buněk včetně kultivace v prostředí cytotoxických látek. V další fázi bude hodnocen genetický profil zjištěných buněk (stanovení panelu 24 genů) a obdobný profil také u histologického preparátu primárního tumoru. Výsledky analýz budou vztaženy na klinický průběh onemocnění a budou stanoveny prognostické faktory účinku léčby na pokles CTC a přežití pacientů.
- MeSH
- analýza přežití MeSH
- diagnostické techniky molekulární MeSH
- exprese genu MeSH
- imunomagnetická separace MeSH
- individualizovaná medicína MeSH
- nádorové buněčné linie cytologie MeSH
- nádorové cirkulující buňky MeSH
- nádory prostaty rezistentní na kastraci diagnóza MeSH
- prognóza MeSH
- prostatický specifický antigen analýza MeSH
- RNA analýza MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biologie
- andrologie
- onkologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Detection of circulating tumor cells (CTC) in patients with castration-resistant prostate cancer (CRPC) may improve the estimate of chemotherapy response. We evaluated the AdnaTest® system in patients receiving docetaxel. PATIENTS AND METHODS: CTC analysis was carried out in 37 patients by immunomagnetic separation. Correlation between serum prostate-specific antigen (sPSA) change and CTC presence and the influence of each parameter on the overall survival (OS) were evaluated. RESULTS: We detected CTCs in 32 and 16 patients before and after three docetaxel cycles, respectively. The sPSA level correlated with CTC positivity during docetaxel therapy (p=0.0031). The longest OS was in patients negative for CTCs in both samples (p=0.0228). Change in sPSA levels was associated with treatment response (p=0.033). CONCLUSION: We detected CTCs in a considerable number of patients with CRPC. The absolute change of sPSA level correlated with OS. CTC presence during docetaxel therapy was associated with shorter OS.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové cirkulující buňky * MeSH
- nádory prostaty rezistentní na kastraci krev patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prognóza MeSH
- prostatický specifický antigen krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- taxoidy terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
