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Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Črevesni mikrobiom predstavlja genetsko zasnovo vseh mikrobov, ki obstajajo v človeškem prebavnem traktu in vsebuje približno 38 bilijonov mikroorganizmov, ki kodira več kot tri milijone genov. Razvoj novih tehnik molekularnega sekvenciranja je omogočil poglobljeno raziskovanje človeškega mikrobioma, ki je vpleten v presnovo hranil, zdravil, vzdržuje celovito bariero črevesne sluznice, varuje pred patogenimi mikroorganizmi in lahko spreminja imunski odziv gostitelja. Vse več je dokazov, da je črevesni mikrobiom vpleten v razvoj nekaterih malignih bolezni in vpliva na učinkovitost onkološkega zdravljenja, predvsem na imunoterapijo. Sedanje razumevanje številnih zapletenih interakcij med črevesnim mikrobiomom, gostiteljevim imunskim sistemom, prehrano, zdravili in malignimi celicami temelji na manjših retrospektivnih in opazovalnih raziskavah. Namen tega prispevka je pregled razpoložljivih podatkov o mikrobiomu in naše dosedanje razumevanje vloge črevesnega mikrobioma pri bolnikih z rakom.

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: As the most common primary malignant intracranial tumor, glioblastoma has a poor prognosis with limited treatment options. It has a high propensity for recurrence, invasion, and poor immune prognosis due to the complex tumor microenvironment. Methods: Six groups of samples from four datasets were included in this study. We used consensus ClusterPlus to establish two subgroups by the EMT-related gene. The difference in clinicopathological features, genomic characteristics, immune infiltration, treatment response and prognoses were evaluated by multiple algorithms. By using LASSO regression, multi-factor Cox analysis, stepAIC method, a prognostic risk model was constructed based on the final screened genes. Results: The consensusClusterPlus analyses revealed two subtypes of glioblastoma (C1 and C2), which were characterized by different EMT-related gene expression patterns. C2 subtype with the worse prognosis had the more malignant clinical and pathology manifestations, higher Immune infiltration and tumor-associated molecular pathways scores, and poorer response to treatment. Additionally, our EMT-related genes risk prediction model can provide valuable support for clinical evaluations of glioma. Conclusions: The assessment system and prediction model displayed good performance in independent prognostic risk assessment and individual patient treatment response prediction. This can help with clinical treatment decisions and the development of effective treatments. [ABSTRACT FROM AUTHOR]

The developments in the field of medicine have led to an increase in human lifespan, but with it comes the growth of older population which is followed by an increase in incidence of neurodegenerative diseases such as Alzheimer’s disease. Until recently, the only available therapy for Alzheimer’s disease was symptomatic in nature, such as the cholinesteraze inhibitors (rivastigmine, donepezil, galantamine) and the NMDA receptor antagonist memantine. Current attempts to find the potential disease-modifying therapy are targeting two typical morphological features of the disease, amyloid plaques and tau protein neurofibrillary tangles, which is why they are classified as anti-amyloid and anti-tau therapy. This approach is based on inhibition of beta-amyloid or tau protein synthesis, prevention of their aggregation or promotion of their clearence through use of specific antibodies. One such drug, aducunumab (brand name Aduhelm), has recently been approved by the FDA for treatment of mild Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction. Although secondary malignancies usually occur at different times after hairy cell leukemia (HCL) treatment, the occurrence of HCL and other malignancies at the same time is very rare. Synchronous HCL and diffuse large B-cell lymphoma (DLBCL) have not been described so far. Case report. The report presents a 62-year-old female patient with intense constitutional symptoms, hypercalcemia, pancytopenia, and osteolytic destruction of the left shoulder joint. Immunohistochemical analysis of the bone marrow revealed the presence of two cell populations: a population of HCL cells and a population of DLBCL cells with the expression of CMYC and BCL-2 proteins ("double expressor" DLBCL) and high proliferative activity (Ki-67+cells > 90%). Fluorescence in situ hybridization (FISH) analysis showed amplification of the BCL-2 gene. In addition, BRAF gene V600E mutation was detected. After intensive treatment with immunochemotherapy, radiotherapy, and bisphosphonates, the patient achieved complete remission, lasting for more than two years. Conclusion. As the association of HCL and lymphoma is very rare, diagnosis of synchronous occurrence of two lymphoproliferative diseases is a diagnostic and therapeutic challenge. It remains unclear whether DLBC and HCL originated from two different malignant clones or DLBCL developed by the transformation of HCL as the result of clonal evolution of the Bcell clone. [ABSTRACT FROM AUTHOR]

Breast carcinoma is the most common malignant disease in the female and one of the leading causes of death among women worldwide. Chronic inflammation and immunosuppressive environment achieved by the interaction of tumour and infiltrating immune cells are the hallmarks of cancers, including breast cancer. Natural killer cells are one of innate immune cells in tumour bed that possess great antitumour potential due to their ability to kill tumour cells without prior sensitization. They also play an important role in priming of type I immune responses and are considered to be main source of Interferon-γ. Unfortunately, antitumour activity of natural killer cells is often suppressed by proinflammatory cytokines secreted in tumour microenvironment and suppression of NK cells activity often correlates with therapy response and general outcome of patient with breast carcinoma. Different types of breast cancer are associated with different subsets of natural killer cells that possess different immunoregulatory function. Identification of specific tumour associated natural killer cell subset endowed with different functional capabilities might help practitioners in therapy decisions, therapy response monitoring, as well as in predicting overall prognosis of breast cancer patients. The purpose of this review is to give an overview of natural killer cells and their subsets, their role in pathogenesis of breast cancer and to discuss NK cells as potential useful therapy and prognostic tool for breast carcinomas. [ABSTRACT FROM AUTHOR]

Pri zdravljenju raka se trenutno uporabljajo pristopi kirurškega zdravljenja, radio- in kemoterapije ter različne kombinacije teh pristopov. Kot 'četrti steber' onkološkega zdravljenja se razvija imunoterapija. Revija Science je imunoterapijo raka že leta 2013 razglasila za 'preboj leta'. Terapije s protitelesi in citokini se uporabljajo že dlje, celična imunoterapija pa pridobiva na pomenu šele v zadnjih letih, še posebej po zaslugi adoptivne T-celične terapije (ATC). Terapije z adoptivnimi limfociti T, kar obravnava prispevek, delimo predvsem na terapije s tumor infiltrirajočimi limfociti (TIL) in terapije z limfociti T, ki so gensko spremenjeni bodisi s transgenimi T-limfocitnimi receptorji (angl. T-cell receptor, TCR) ali pa s himernimi antigenskimi receptorji (CAR). Vse te terapije so izrazito personalizirane in trenutno temeljijo na presaditvi avtolognih, t.j. bolnikovih lastnih celic. Terapevtiki se pripravijo za vsakega bolnika posebej, kar zelo vpliva na procese razvoja in izdelave ter tako na logistiko in stroške, ki so povezani s tem. Nov način terapij s CAR-T, ki je za določene bolezni trenutno tudi edini registrirani način ATC, povzroča revolucionarne premike pri razvoju takih naprednih terapevtikov, s tem pa tudi v klinični onkologiji. Terapija s CAR-T dosega izredne uspehe v klinični praksi zlasti v boju proti hematološkim oblikam raka, medtem ko pri zdravljenju bolnikov s solidnimi tumorji še ne. Hkrati pa zaradi velike kompleksnosti terapije težavo pri zdravljenju s CAR-T povzročajo pogosti, težki stranski učinki, ki lahko vodijo tudi v bolnikovo smrt. Z ustreznimi ukrepi lahko stranske učinke nadzorujemo in delno ublažimo. Terapija s CAR-T vstopa v Slovenijo s komercialno dostopnimi terapevtiki te vrste, na možnost ostalih adoptivnih celičnih terapij pa bo potrebno še počakati. V Sloveniji pa na tem področju razvijamo tudi lastno znanje in tehnologijo, zato upamo, da bodo novi učinkoviti načini zdravljenja čim prej dostopni čim širšemu krogu bolnikov.

Over the last 10-15 years, the prognosis of patients with follicular lymphoma has improved, and for the majority of patients, follicular lymphoma is a chronic disease with ten years of overall survival of around 80%. Nevertheless, a certain subset of patients belongs to high-risk follicular lymphoma with early relapses and progressive disease, poor outcomes, and much shorter survival, and there is still no standard approach in the treatment of high-risk follicular lymphoma. Treatment of follicular lymphoma is highly heterogeneous, ranging from a „watch and wait” strategy to intensive immunochemotherapy, and needs to be individualized to each patient. An early stage of the disease can be treated with involved-field radiotherapy, which has curative potential. Follicular lymphoma in the advanced stage is still an incurable disease. Standard first-line treatment is a combination of an anti-CD20 antibody (rituximab) and chemotherapy, followed by antibody maintenance. In relapse, treatment with novel anti-CD20 monoclonal antibody-obinutuzumab in combination with chemotherapy. The combination of lenalidomide and rituximab shows good results in patients with relapses and refractory follicular lymphoma, but also as a first-line treatment. An option for elderly patients with comorbidities is rituximab monotherapy. Autologous or allogeneic stem cell transplantation may be an option for a small group of selected patients. In the past decade development of novel targeted agents such as phosphoinositide three kinase inhibitors and immunotherapies (CD20/CD3 bispecific antibody, chimeric antigen receptor T cell therapy) demonstrate the efficiency of chemotherapy-free approach not only for relapsed/refractory patients but also in first-line treatment. A better understanding of the clinical and biological features of follicular lymphoma patients is necessary to improve treatment outcomes in the future [ABSTRACT FROM AUTHOR]

With regard to systemic oncological treatments, correlation of the use of immunotherapy with checkpoint inhibitors with the risk of more severe COVID-19 infection is uncertain. However, benefits of immunotherapy in the disease caused by the new coronavirus completely suppressed the initial fear of expected negative impacts of immune system triggered by checkpoint inhibitors. By preventing CD8 + lymphocyte exhaustion, reducing interleukin-6 levels, and indirectly regulating neutrophils and NK cells, immunotherapy affects the pathophysiology of COVID-19. The current findings highlight immunotherapy as a safe option of cancer treatment at the time of COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have already proved their effectiveness in the treatment of various forms of cancer, and every day their use is becoming more and more prevalent. Unfortunately, any effective treatment has side effects, and immunotherapy is no exception. In this article, the authors review the history of immune checkpoint inhibitors, their mechanism of action, indications, and complications of their use, with particular focus on neurologic complications. These, although relatively rare, are potentially life-threatening, so a thorough investigation and prompt treatment with glucocorticoids or other immunosuppressive medications is of an utmost importance. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis (AE) is a group of inflammatory brain disorders involving the central nervous system (CNS) that currently includes more than 10 distinct types of the disease. Nowadays, AE has been identified as the second most frequent cause of encephalitis after infectious etiology. Over the past decade, the clinical spectrum of AE has expanded, and new clinicopathological entities are increasingly being identified. Also, our understanding of disease mechanisms and treatment strategies is rapidly evolving. In clinical practice, neuronal antibodies remain the most significant diagnostic marker currently available. Prognosis of AE varies greatly depending on the subtype and the time of immunotherapy initiation. In general, AE patients respond well to immunotherapy, therefore cognitive functions might be fully or at least partially restored. Cumulative research on the AE pathogenesis has resulted in a paradigm shift in clinical decision-making for these patients. In this article, we present two clinical cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) and anti-contactin-associated protein-like 2 (anti-CASPR2) encephalitides and focus on the essential aspects of these conditions based on the latest scientific literature. [ABSTRACT FROM AUTHOR]

Izhodišča: Imunoterapija z zaviralcem imunskih kontrolnih točk nivolumabom, zaviralnim protitelesom proti proteinu programirane celične smrti 1 (PD-1), predstavlja za bolnike z neozdravljivo ponovitvijo bolezni ali s sistemskimi zasevki ploščatoceličnega karcinoma glave in vratu (P/Z PKGV), pri katerih je bolezen neobčutljiva na preparate platine, pomembno novo možnost zdravljenja. V primerjavi s citostatiki pomembno podaljša njihovo preživetje. Metode: Retrospektivna analiza zdravljenja z nivolumabom pri slovenskih bolnikih s P/Z PKGV, ki so prejeli prvi odmerek nivolumaba do marca 2020. Zbiranje podatkov je bilo zaključeno v septembru 2020. Uporabljene so bile opisne statistične metode in log-rank test. Rezultati: V raziskavo je bilo vključenih 27 bolnikov. Srednji čas sledenja od prve aplikacije nivolumaba do konca opazovanja je bil 7,4 meseca, relativno šestmesečno celokupno preživetje pa 59% (95% interval zaupanja 41–78%). Odgovor na zdravljenje je bil pri 85% bolnikov ocenjen s kliničnim pregledom in rentgenskim slikanjem prsnega koša, pri čemer je bil pri 41% kot najboljši odgovor ugotovljen delen odgovor na zdravljenje. Imunsko pogojeni neželeni dogodki so se pojavili pri 30% bolnikov, pri čemer so bili vsi gradusa ≤2. En bolnik je bil sočasno z nivolumabom tudi obsevan. Zaključek: Glede na zbrane podatke se je tudi v slovenski populaciji bolnikov s P/Z PKGV zdravljenje z nivolumabom izkazalo za varno. Zaradi kratkega časa sledenja ugotovljene učinkovitosti ni mogoče primerjati z rezultati tujih raziskav. S pričakovano odobritvijo pembrolizumaba bodo zaviralci imunskih kontrolnih točk tudi v Sloveniji dobili mesto v prvem redu zdravljenja P/Z PKGV.

U novijoj medicini sve više se pristupa imunoterapiji kojoj je cilj potaknuti stanice imunološkog sustava da uoče i unište zloćudne stanice kako bi se pokrenuo obrambeni proces. Imunološke stanice se mogu proizvesti u laboratoriju pod kontroliranim uvjetima, te kao takve dati pacijentima. Jedna od odobrenih imunoterapija je revolucionarna Car T-cell terapija. To je vrsta liječenja koja programira pacijentove vlastite izmijenjene bijele krvne stanice kako bi se uništile one zloćudne. U Sjedinjenim Američkim Državama, 2012. godine je prvo dijete eksperimentalno primilo Car T-cell terapiju. Od 18. 11. 2019. godine KBC Zagreb je, nakon niza edukacija, izabran i ovlašten za provođenje terapije u Hrvatskoj, a prema potrebi i u regiji. Sam postupak dobivanja lijeka je kompleksan. Aferezom se prikupljaju pacijentovi T limfociti te ih se šalje u centar za izradu lijeka u SAD-u. Ondje se limfociti genetski modificiraju i dobije se lijek koji nakon jednog infundiranja pronalazi zloćudne stanice i uništava ih. Za primjenu terapije kandidati su pedijatrijski i mladi odrasli bolesnici do 25 godina s ALL B stanica koja je refraktorna, u recidivu nakon transplantacije, te odrasli bolesnici s recidivirajućim ili refraktornim difuznim B velikostaničnim limfomom (DLBCL). Ozbiljne nuspojave javljaju se u većine bolesnika, međutim mogu se liječiti. Zaključeno je da koristi od lijeka nadmašuju s njim povezane rizike te da lijek može biti odobren za primjenu te predstavlja budućnost u liječenju djece i mladih. [ABSTRACT FROM AUTHOR]

Interakcija med tumorskimi celicami in imunskimi celicami v tumorski stromi je pomembna za nastanek, razvoj in progresijo raka. Pri raku dojk je najbolj preučena vloga tumorskega limfocitnega infiltrata (TIL) in izraženosti liganda za programirano smrt-1 (PD-L1). Večja izraženost TIL je neodvisni napovedni dejavnik za dosego popolne patološke remisije po neoadjuvantni sistemski terapiji pri HER2+ in trojno negativnem podtipu raka dojk in za celotno preživetje pri trojno negativnem raku dojk. Največ raziskav z zaviralci kontrolnih točk (imunoterapijo) poteka pri metastaskem trojno negativnem raku dojk. V klinični praksi se že uporablja atezolizumab v kombinaciji z nab-paklitakselom pri primarno metastatskih bolnicahh in tistih s progresom več kot 12 mesecev po adjuvantni terapiji, če imajo prekomerno izražen PD-L1. Še vedno pa se raziskuje, kateri mehanizmi in biomarkerji so udeleženi pri reakciji imunskega sistema na tumor, saj ima le majhen delež bolnikov dolgotrajno dobrobit od imunoterapije.

Karcinom Merklovih celic (KMC) je redek, agresiven nevroendokrini kožni rak s slabo prognozo, posebno, ko je v napredovalem stadiju. Incidenca na splošno narašča, čeprav podatki o incidenci kažejo na razlike med geografskimi področji. Med dejavnike tveganja štejemo starost, imunosupresijo in izpostavljenost ultravijoličnemu sevanju. Znana je povezava med MCC in okužbo s poliomavirusom, čeprav natančnega mehanizma, ki vodi v karcinogenezo, še ne razumemo v celoti. Pri lokalizirani bolezni je izbor zdravljenja kirurgija (ko je to mogoče), sledi mu dopolnilno obsevanje ali obsevanje v kombinaciji s kemoterapijo. Pri razsejani bolezni je bila doslej na voljo le kemoterapija, čeprav so dolgotrajni odgovori ob njej redki. Glede na to, da je onkogeneza tumorja povezana z integracijo poliomavirusa Merklovih celic in mutacijami, povzročenih z ultravijoličnim sevanjem, obstaja logična osnova za zdravljenje z imunoterapijo oz. protitelesi, ki ciljajo pot PD-L1/PD-1. Nedavno objavljene raziskave v prvem in drugem redu zdravljenja z inhibitorji imunskih stikal (anti-PD-1/PD-L1-protitelesi) kažejo obetajoče rezultate s sprejemljivim varnostnim profilom zdravljenja, zato tovrstno zdravljenje postaja standardno in je že priporočeno v mednarodnih smernicah za zdravljenje razsejanega raka Merklovih celic. Objavljeni podatki randomiziranih raziskav kažejo na obetajočo učinkovitost teh zdravil pri metastatski bolezni.

Imunoterapija je v zadnjih letih postala eden izmed pomembnih načinov sistemskega zdravljenja bolnikov z rakom. Priča smo bili različnim imunskim strategijam, med temi je tudi inhibicija kontrolnih točk. Zdravila proti CTLA-4, PD-1 in PD-L1 so protitelesa proti zaviralcem kontrolnih točk, ki lahko povišajo imunsko aktivnost proti rakavim celicam in tako ojačajo imunski odgovor proti raku. Večja uporaba teh zdravil pa je privedla do pojava posebne vrste imunsko pogojenih neželenih učinkov. Ti se najpogosteje izrazijo na koži, črevesju, žlezah z notranjim izločanjem, pljučih in mišično-skeletnem sistemu, lahko pa je prizadet kateri koli organ. Večina imunsko pogojenih neželenih učinkov je blagih do zmernih, v literaturi pa obstajajo poročila o hudih in življenje ogrožajočih. Pomembna je njihova zgodnja prepoznava in zdravljenje, kakor tudi multidisciplinaren pristop, da preprečimo resne zaplete.

Copyright of Onkologija is the property of Institute of Oncology Ljubljana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Začetni poskusi zdravljena z imunoterapijo segajo v leto 1893. Skoraj stoletje kasneje pa so bila odobrena prva zdravila, ki jih štejemo med imunoterapijo, kot sta interferon in interlevkin. Vlogo imunskega sistema pri raku znanstveniki v zadnjih letih razlagajo s pomočjo protitumorskega imunskega cikla. V prvem koraku tega cikla pride do sproščanja tumorskih antigenov (neoantigenov), ki jih antigen predstavitvene celice spoznajo in ujamejo. V drugem koraku jih v bezgavkah predstavijo celicam T. Za aktivacijo in determinacijo celic T v smeri citotoksičnih T-celic je potreben še dodaten stimulatorni signal. Morebitni inhibitorni signali pa aktivacijo celic T zavirajo oz. preprečujejo čezmerno aktivacijo in avtoimunost. Aktivirane celice T po krvi potujejo v tumor. Tumorsko celico prepoznajo prek T-celičnega receptorja. S tem preide do uničenja tumorske celice. V sami tumorski stromi pa so lahko različni inhibitorni signali, ki delovanje citotoksičnih celic T onemogočijo. V prispevku so predstavljeni možni načini vplivanja na protitumorski imunski cikel in trenutno registrirana zdravila s področja imunoterapije.

Protein programirane celične smrti 1:PD-1 (Programmed cell death protein 1) je transmembranski protein, ki je izražen na celicah T, B, NK ter monocitih in dendritičnih celicah. Vezava med PD-1 in njegovimi ligandi zavira tumorsko celično apoptozo, spodbuja izčrpanost T-celic in preprečuje aktiven antitumorski odziv, kar posledično omogoča nemoteno rast in razvoj tumorskih celic. Zaviralca receptorja PD-1, pembrolizumab in nivolumab, že uporabljamo v zdravljenju različnih vrst napredovalega raka, kot so: melanom, nedrobnocelični karcinom pljuč, Hodgkinov limfom in karcinom ledvic. Na zdravljenje odgovori zelo različno število bolnikov, kar je odvisno od indikacije in linije zdravljenja, to je od pri 18 do 80 odstotkih bolnikov. Posebnosti zdravljenja z imunoterapijo so zelo dolgotrajne remisije, pri posameznih bolnikih pa bomo morebiti upali govoriti celo o ozdravitvi. Najpogostejši neželeni učinki so utrujenost, srbečica, izpuščaji, driska in slabost. Najresnejši neželeni učinki so imunsko pogojeni neželeni učinki in hude z infuzijo povezane reakcije. Imunsko pogojeni neželeni učinki so kolitis, tiroiditis, pneumonitis, hepatitis in nefritis.

V zadnjih petnajstih letih smo priča hitremu razvoju na področju zdravljenja pljučnega raka, ki ostaja v svetovnem merilu še vedno rak z najvišjo obolevnostjo in umrljivostjo. Večina bolnikov z metastatsko boleznijo se zdravi s kemoterapijo (KT), tarčno zdravljenje je primerno za manj kot 20% bolnikov z nedrobnoceličnim pljučnim rakom (NDPR). V letu 2010 so nas navdušili rezultati raziskav na področju imunoterapije. Tumorske celice morajo biti prepoznane kot tuje telesu, da jih imunski sistem lahko odstrani. Vendar so tumorske celice razvile različne mehanizme za izmikanje imunskemu nadzoru, eden od teh je tudi sproščanje imunskih zaviralnih molekul kot je ligand programirane celične smrti (PD-L1), ki je glavni mediator imunosupresivnega delovanja. Zdravila, ki se trenutno uporabljajo za zdravljenje metastatskega NDPR, so monoklonska protitelesa proti PD-L1 ali PD-1. Z vezavo na PD-L1 ali njegov receptor PD-1 na imunskih celicah preprečijo imunosupresiven učinek in omogočijo uspešno delovanje aktiviranih T limfocitov. V Sloveniji sta registrirani dve zdravili z opisanim načinom delovanja, nivolumab in pembrolizumab. Na kongresu ESMO 2017 pa so bili predstavljeni rezultati raziskave PACIFIK, ki opisujejo dobrobit zdravljenja z imunoterapijo tudi pri lokalno napredovalih bolnikih z NDPR. Bolniki so po standardnem zdravljenju s kemoradioterapijo prejemali durvalumab ali placebo. V skupini, zdravljeni z durvalumabom, je bil čas brez napredovanja bolezni značilno daljši. Sinergistično delovanje obsevanja, ki je splošno priznan način lokalnega zdravljenja, v kombinaciji z imunoterapijo briše meje med sistemskim in lokalnim načinom zdravljenja raka, kar so pokazale tudi številne predklinične raziskave. Bodoče raziskave bodo podale odgovore, kateri način kombiniranja imunoterapije in obsevanja je najbolj primeren.

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Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dendritic cells (DCs) are the key antigen-presenting cells and stimulators of the immune response. Numerous studies have proven DC-based tumor vaccines as the most effective form of tumor vaccines with good results in clinical trials. Due to the marked disproportion in the results of complete tumor curing in some patients using DC-based vaccines and modest results achieved in other patients, there is a need for improvement of preparation methods. This review summarizes the current protocols in creating DC-based tumor vaccines and future perspectives as well. [ABSTRACT FROM AUTHOR]

Copyright of Vilnius University Proceedings is the property of Vilnius University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)