Photodynamic therapy (PDT) is an encouraging procedure for treatment and diagnosis of a wide variety of malignant processes. There are three main mechanisms by which tumors are destroyed during PDT: direct cell destruction, damage to the vascular stroma and immune elimination. PDT of high intensity, targeted to a large number of cells results in immunosuppression. Low dose/energy or localized PDT stimulates the immune response against the tumor. The review reports recently performed animal experimental studies as well as the first human clinical studies.

• MeSH
• buněčná imunita * MeSH
• fotochemoterapie * MeSH
• lidé MeSH
• nádory farmakoterapie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Photodynamic therapy (PDT) is a new modality in cancer treatment. It is based on the tumour-selective accumulation of a photosensitizer followed by irradiation with light of a specific wavelength. PDT is becoming widely accepted owing to its relative specificity and selectivity along with absence of the harmful side-effects of chemo and radiotherapy. There are three known distinct mechanisms of tumour destruction following PDT, generation of reactive oxygen species which can directly kill tumour cells, tumour vascular shutdown which can independently lead to tumour destruction via lack of oxygen and nutrients and thirdly enhanced antitumour immunity. METHODS: A review based on the literature acquired from the PubMed database from 1983 with a focus on the enhanced antitumour immunity effects of PTD. RESULTS AND CONCLUSION: Tumour cell death is accompanied by the release of a large number of inflammatory mediators. These induce a non-specific inflammatory response followed by gradual adaptive antitumour immunity. Further, a combination of PDT with the immunological approach has the potential to improve PDT efficiency and increase the cure rate. This short review covers specific methods for achieving these goals.

• MeSH
• adaptivní imunita účinky léků   MeSH
• aktivace komplementu MeSH
• cytokiny metabolismus   MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky terapeutické užití   MeSH
• imunologická tolerance MeSH
• lidé MeSH
• nádory farmakoterapie   imunologie   MeSH
• oxidační stres MeSH
• přirozená imunita účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• fotosenzibilizující látky MeSH

Non-small cell lung cancer (NSCLC) is largely promoted by a multistep tumorigenesis process involving various genetic and epigenetic alterations, which essentially contribute to the high incidence of mortality among patients with NSCLC. Clinical observations revealed that NSCLC also co-opts a multifaceted immune checkpoint dysregulation as an important driving factor in NSCLC progression and development. For example, a deregulated PI3K/AKT/mTOR pathway has been noticed in 50-70% of NSCLC cases, primarily modulated by mutations in key oncogenes such as ALK, EGFR, KRAS, and others. Additionally, genetic association studies containing patient-specific factors and local reimbursement criteria expose/reveal mutations in EGFR/ALK/ROS/BRAF/KRAS/PD-L1 proteins to determine the suitability of available immunotherapy or tyrosine kinase inhibitor therapy. Thus, the expression of such checkpoints on tumors and immune cells is pivotal in understanding the therapeutic efficacy and has been extensively studied for NSCLC treatments. Therefore, this review summarizes current knowledge in NSCLC tumorigenesis, focusing on its genetic and epigenetic intricacies, immune checkpoint dysregulation, and the evolving landscape of targeted therapies. In the context of current and future therapies, we emphasize the significance of antibodies targeting PD-1/PD-L1 and CTLA-4 interactions as the primary therapeutic strategy for immune system reactivation in NSCLC. Other approaches involving the promising potential of nanobodies, probodies, affibodies, and DARPINs targeting immune checkpoints are also described; these are under active research or clinical trials to mediate immune regulation and reduce cancer progression. This comprehensive review underscores the multifaceted nature, current state and future directions of NSCLC research and treatment.

• Klíčová slova
• CTLA-4, NSCLC, PD-1, PD-L1, immune checkpoint, targeted therapy,
• MeSH
• antigeny CD274 metabolismus   MeSH
• erbB receptory metabolismus   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• karcinogeneze MeSH
• lidé MeSH
• nádorová transformace buněk MeSH
• nádory plic * farmakoterapie   genetika   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   genetika   MeSH
• protoonkogenní proteiny p21(ras) MeSH
• tyrosinkinasové receptory metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny CD274 MeSH
• erbB receptory MeSH
• fosfatidylinositol-3-kinasy MeSH
• protoonkogenní proteiny p21(ras) MeSH
• tyrosinkinasové receptory MeSH

Introduction: The expiry of patents for biologics has led to the introduction of biosimilars for the treatment of immune-mediated inflammatory diseases (IMIDs). These treatment alternatives may allow earlier and wider access to appropriate therapy for patients without increasing the economic burden on health-care systems. Prescription of biosimilars to treatment-naïve patients is well accepted; however, additional considerations must be taken into account when switching clinically stable patients from reference products to biosimilars. Area covered: We discuss the current considerations related to switching from reference products to biosimilars from a physician and patient perspective. We review the clinical data and real-life experience on switching patients with IMIDs, present the position of the relevant medical societies, and discuss the importance of patient-physician communication and need for shared decision-making. Expert opinion: The introduction of biosimilars provides an opportunity to expand access to treatment for patients with IMIDs across Europe and support the financial sustainability of health-care systems. We anticipate that as the real-world evidence base grows, confirming the results of clinical trials, there will be a corresponding increase in physician and patient acceptance, not only to initiating treatment with a biosimilar, but also to switching medication from a reference product to a biosimilar.

• Klíčová slova
• Biological therapy, biosimilar, immune-mediated inflammatory disease, switching,
• MeSH
• biosimilární léčivé přípravky terapeutické užití   MeSH
• lidé MeSH
• nemoci imunitního systému farmakoterapie   genetika   imunologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biosimilární léčivé přípravky MeSH

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells that has been recognized as a disease responsive to immunotherapy. Despite the huge success of the tyrosine kinase inhibitors (TKIs), CML remains for the most part incurable, probably due to treatment resistance of leukemic stem cells, which are responsible for rapid disease relapse after discontinuation of therapy. Only allogeneic stem cell transplantation enables disease eradication. In addition to the Bcr-Abl1 oncoprotein, TKIs also inhibit off-target kinases (e.g. c-kit, Src, Tec), some of them having physiological functions in immune responses. In vitro studies have implied immunomodulatory effects of TKIs and interferon-alpha (IFN-α), but comprehensive information from in vivo analyses is missing. This review summarizes the recent advances in the field of immunology of CML, including basic information about leukemia-associated antigens and peptide vaccines, that could lead to the incorporation of TKIs and IFN-α in future therapeutic, potentially curative, interventions for CML.

• MeSH
• antigeny nádorové chemie   imunologie   MeSH
• chronická myeloidní leukemie imunologie   terapie   MeSH
• imunitní systém účinky léků   imunologie   MeSH
• imunologické faktory terapeutické užití   MeSH
• imunoterapie MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• interferon alfa metabolismus   terapeutické užití   MeSH
• lidé MeSH
• protinádorové vakcíny imunologie   terapeutické užití   MeSH
• signální transdukce účinky léků   MeSH
• subjednotkové vakcíny imunologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny nádorové MeSH
• imunologické faktory MeSH
• inhibitory proteinkinas MeSH
• interferon alfa MeSH
• protinádorové vakcíny MeSH
• subjednotkové vakcíny MeSH

Even though an association between inflammation and hypertension has been known for many years, it has not been simple to ascertain the role of several physiological responses involved. The innate immune response plays a critical role in these physiological responses. Innate immune cells can be activated directly by shear stress, activate the inflammasome and produce numerous cytokines and soluble mediators essential in hypertension. NFkB activation is mainly involved in the activation of innate immune cells. Shear stress also stimulates the expression of DAMP and PAMP receptors, enhancing pathogen and danger signals and magnifying inflammation. The adaptative immune response is activated with the increased antigen presentation resulting from the insults mentioned. Chronic inflammation may lead to autoimmunity. Peripheral hypoxia, a consequence of hypertension, activates hypoxia-inducing factors 1-α and 1-β (HIF-1α, HIF-1β), which modulate innate immune cells and promote inflammation. HIF-1α is involved in the upregulation of oxygen and nitrogen radical production proteins. HIF-1β down-regulates antioxidant enzymes. However, the critical evidence of the role of innate immune cells in hypertension came from the results of clinical trials involving therapies blocking inflammatory cytokines and Toll-like receptor expression. Several lines of research have been conducted on this complex disease. Pro-tolerogenic innate immune cells, myeloid suppressor cells, and M2 macrophages may play a crucial role in promoting or resolving inflammation, cardiovascular diseases and hypertension, and should be studied in detail.

• Klíčová slova
• Sodium transport, antihypertensive therapy, hypertension, hypoxia, inflammasome, innate immune response, toll-like receptors,
• MeSH
• cytokiny metabolismus   MeSH
• hypertenze * MeSH
• hypoxie MeSH
• lidé MeSH
• přirozená imunita * MeSH
• zánět metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH

BACKGROUND: Allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are at high risk of complications associated with COVID-19 infection due to dysfunction of their immune system. Vaccination can protect from the adverse consequences of COVID-19. However, studies on the efficacy of COVID-19 vaccines in HSCT recipients with insufficient post-HSCT immune reconstitution are still scarce. In our study, we determined how immunosuppressive medication and the reconstitution of the cellular immune system influenced T cell responses specific for the surface glycoprotein of SARS-CoV-2 virus (S antigen) after two doses of mRNA vaccine against COVID-19 in patients with myeloid malignancies treated with HSCT. METHODS: Vaccination outcomes were followed in 18 (allo-HSCT) recipients and 8 healthy volunteers. The IgG antibodies against SARS-CoV-2 spike (S) and nucleocapsid (NCP) protein were determined in ELISA and S-specific T cells were detected using a sensitive ELISPOT-IFNγ based on in vitro expansion and restimulation of T cells in pre- and post-vaccination blood samples. Multiparametric flow cytometry analysis of peripheral blood leukocyte differentiation markers was employed for determination of reconstitution of the main subpopulations of T cells and NK cells at month 6 after HSCT. RESULTS: S- specific IgG antibody response detected in 72% of the patients was lower than in healthy vaccinees (100%). Vaccine-induced T-cell responses to S1 or S2 antigen were significantly reduced in HSCT recipients, which were treated with corticosteroids in dose 5 mg of prednisone- equivalents or higher during the vaccination period or in preceeding 100 days in comparison with recipients un-affected with corticosteroids. A significant positive correlation was found between the level of anti-SARS-Cov-2 spike protein IgG antibodies and the number of functional S antigen-specific T cells. Further analysis also showed that the specific response to vaccination was significantly influenced by the interval between administration of vaccine and transplantation. Vaccination outcomes were not related to age, sex, type of mRNA vaccine used, basic diagnosis, HLA match between HSC donor and recipient, and blood counts of lymphocytes, neutrophils, and monocytes at the time of vaccination. Multiparametric flow cytometry analysis of peripheral blood leukocyte differentiation markers showed that good humoral and cellular S-specific immune responses induced by vaccination were associated with well-reconstituted CD4+ T cells, mainly CD4+ effector memory subpopulation at six months after HSCT. CONCLUSIONS: The results showed that both humoral and cellular adaptive immune responses of HSCT recipients to the SARS-CoV-2 vaccine were significantly suppressed by corticosteroid therapy. Specific response to the vaccine was significantly affected by the length of the interval between HSCT and vaccination. Vaccination as early as 5 months after HSCT can lead to a good response. Immune response to the vaccine is not related to age, gender, HLA match between HSC donor and recipient, or type of myeloid malignancy. Vaccine efficacy was dependent on well-reconstituted CD4+ T cells, at six months after HSCT.

• Klíčová slova
• Allogeneic hematopoietic stem cell transplantation, Antibodies, COVID-19, Immune reconstitution, SARS-Cov-2, T cells, Vaccination,
• MeSH
• COVID-19 * prevence a kontrola   MeSH
• imunita MeSH
• imunoglobulin G MeSH
• imunosupresivní léčba MeSH
• lidé MeSH
• mRNA vakcíny MeSH
• nádory * MeSH
• SARS-CoV-2 MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• vakcíny proti COVID-19 MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imunoglobulin G MeSH
• mRNA vakcíny MeSH
• vakcíny proti COVID-19 MeSH

OBJECTIVE: To investigate the impact of growth hormone (GH) therapy in adults with childhood-onset GH deficiency on immune system. METHODS: Ten young GH deficient adults (7 males, age 19-28 years) were treated with recombinant human growth hormone for 6 months. The starting dose was 0.5 IU/m2/day (2 weeks), then it was doubled to 1.0 IU/m2/day. In 5/10 patients, the dose was further increased to 1.5 IU/m2/day at 4 weeks of therapy. Immunological studies were performed before treatment and after 6 weeks, 3 months and 6 months and included humoral (IgG, IgA, IgM, C3, C4 and immune complexes) and cellular parameters (total lymphocyte count and counts of CD3+, CD4+, CD8+ and CD19+ lymphocytes, the CD4+/CD8+ ratio and percentage of CD16+56+ and CD3+DR+). RESULTS: The cellular responses to GH therapy were subtle, but detectable, with the trend to the higher CD4+ and lower CD8+ lymphocytes and maximal changes at 6 months of therapy. They were reflected in CD4/CD8 ratio, which increased from 1.15 +/- 0.10 (mean +/- S.E.; baseline) to 1.37 +/- 0.11 (6 weeks; P < 0.05), 1.24 +/- 0.10 (3 months; n.s.) and to 1.59 +/- 0.20 (6 months; P < 0.05). The response in humoral immunity was characterized by a rapid decrease of circulating immunoglobulins (IgA: 1.40 +/- 0.25 g/l [mean+/-S.E.], baseline; 1.12 +/- 0.19, at 6 weeks; P < 0.05) and C4 (0.25 +/- 0.02 g/l, baseline; 0.19 +/- 0.01, at 6 weeks; P < 0.05) and a tendency to an increase in circulating immune complexes (29.1 +/- 8.1, baseline; 40.3 +/- 7.2, at 6 weeks; n.s.). These observations suggest a temporary immune complex formation after the onset of GH treatment which might play a partial role in developing oedema as a side effect of GH treatment, besides the known effect of GH on water retention. CONCLUSIONS: GH therapy in GH deficient young adults has a measurable effect on the increase of CD4/CD8 ratio and on the formation of immune complexes.

• MeSH
• dospělí MeSH
• hypofyzární nanismus farmakoterapie   imunologie   MeSH
• imunoglobuliny krev   MeSH
• imunokomplex krev   MeSH
• lidé MeSH
• počet lymfocytů MeSH
• poměr CD4 a CD8 lymfocytů MeSH
• růstový hormon terapeutické užití   MeSH
• tvorba protilátek MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobuliny MeSH
• imunokomplex MeSH
• růstový hormon MeSH

INTRODUCTION: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD. METHODS: We contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs. RESULTS: In this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades ≥ 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI. DISCUSSION: This European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.

• Klíčová slova
• PD-1/PD-L1 immune checkpoint inhibitors, autoimmune disease (AID), autoimmune hepatitis (AIH), autoimmune liver diseases (AILD), immune checkpoint inhibitors (ICI), immune related adverse effects (irAEs), primary biliary cholangitis (PBC), primary sclerosing cholangites (PSC),
• MeSH
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• autoimunitní hepatitida * farmakoterapie   MeSH
• cholestáza * MeSH
• inhibitory kontrolních bodů škodlivé účinky   MeSH
• lidé MeSH
• nádory * MeSH
• nivolumab škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD274 MeSH
• antigeny CD279 MeSH
• inhibitory kontrolních bodů MeSH
• nivolumab MeSH

A combination of penicillin and cloxacillin (Ampiclox, Beecham Research Laboratories) is indicated for prophylaxis and treatment of bacterial infections in premature babies or neonates. We studied the functional development of the immune system in the offspring of female ICR mice administered Ampiclox on days 13-16 of pregnancy in clinically relevant doses. Immune functions were assayed after immunization with sheep red blood cells in the 5th and 10th postnatal week. Changes of hemagglutinin antibodies, delayed-type hypersensitivity and proliferative responses of spleen lymphocytes and thymocytes were observed. Ampiclox influenced humoral immunity also when administered directly to rat young on postnatal days 9-11 or 14-16. Although the clinical relevance of our experimental data remains to be established an increased sensitivity of the developing immune system to immunomodulatory effects should be considered also in the context of antimicrobial therapy. (Fig. 6, Ref. 27.)

• MeSH
• aktivace lymfocytů účinky léků   MeSH
• ampicilin farmakologie   MeSH
• imunita účinky léků   MeSH
• kloxacilin farmakologie   MeSH
• kombinovaná farmakoterapie farmakologie   MeSH
• myši inbrední ICR MeSH
• myši MeSH
• pozdní přecitlivělost MeSH
• tvorba protilátek účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ampicilin MeSH
• kloxacilin MeSH
• Viccillin S (combination) MeSH Prohlížeč