Title Imunoterapija u liječenju tumora glave i vrata Title (english) Immunotherapy in the treatment of head and neck tumors Author Morana Belović Mentor Marin Prpić (mentor)Committee member Jasmina Marić Brozić (predsjednik povjerenstva)Committee member Lovorka Batelja-Vuletić (član povjerenstva)Committee member Marin Prpić (član povjerenstva)Granter University of Zagreb Defense date and country 2023-09-19, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Tumori glave i vrata skupina su maligniteta porijeklom iz mnogoslojnog pločastog epitela koja zahvaća gornji aerodigestivni trakt. Nalaze se u prvih deset najčešćih karcinoma, a njihova incidencija je u porastu uslijed raširenosti i učestalosti rizičnih faktora koji promiču njihov nastanak. Tradicionalno, primarni modalitet liječenja ove skupine tumora bila je kirurška operacija uz adjuvantnu radioterapiju, odnosno primarna radioterapija, međutim obje su metode dovodile do visokog stupnja mutilacije i smanjenja kvalitete života pacijenata, pogotovo u slučaju lokalno proširenih i metastatskih tumora. Napretkom imunologije kao znanosti, otkriveno je da su tumori općenito, a posebice tumori glave i vrata, imunološki vrlo aktivna tkiva, s burnim odgovorom imunosnog sustava na prisutnost tumorskih stanica. Na osnovu toga, razvijen je novi terapijski modalitet s ciljem djelovanja na imunosne stanice u tumorskom mikrookolišu – imunoterapija. Tip imunoterapije u kliničkoj upotrebi u liječenju tumora glave i vrata su inhibitori imunosnih kontrolnih točaka, konkretno inhibitori PD-1 (eng. Programmed Death 1) signalnog puta. Ovaj rad prikazuje pregled tumorske imunosti kao osnove za imunoterapiju, te specifičnosti izuzetno imunosno aktivnog tumorskog mikrookoliša u tumorima glave i vrata, na osnovu koje je i započela klinička primjena imunoterapije u liječenju ovih malignih bolesti. Razrađena je problematika same imunoterapije kao novog i još često eksperimentalnog terapijskog modaliteta; spomenuti su svi njezini oblici, s posebnim naglaskom na terapiju PD-1 inhibitorima, koja se primjenjuje u tumorima glave i vrata. Navedeni su i neželjeni događaji vezani uz primjenu PD-1 inhibitora, primatno štetni učinci odnosno nuspojave te razvoj rezistencije. Od štetnih su učinaka najznačajniji oni specifični za imunoterapiju; iako relativno rijetki, mogu uzrokovati ozbiljne i dugotrajne zdravstvene probleme. Razvoj rezistencije predstavlja jedan od najvećih problema pri liječenju imunosno aktivnim spojevima; mogući uzroci ove pojave su brojni, a kriju se kako u prirodi tumorskog tkiva, tako i u fiziologiji samih pacijenata. Kako bi se doskočilo spomenutim nedostacima primjene imunoterapije, ekstenzivno se istražuju kombinacije s drugim terapijskim modalitetima uobičajenima za liječenje malignih bolesti; neke se od njih već primjenjuju, dok su druge tek u ranim fazama ispitivanja.
Abstract (english) Head and neck tumors are a group of malignancies originating from the stratified squamous epithelium and affecting the upper aerodigestive tract. They are in the top ten most common cancers, and their incidence is increasing due to the prevalence and frequency of risk factors that promote their occurrence. Traditionally, the primary treatment modality for this group of tumors was surgery with adjuvant radiotherapy, i.e. primary radiotherapy; however, both methods led to a high degree of mutilation and reduced quality of life for patients, especially in the case of locally advanced and metastatic tumors. With the progress of immunology, it was discovered that tumors in general, and head and neck tumors in particular, are very immunologically active tissues, with an extensive response of the immune system to the presence of tumor cells. Based on this, a new therapeutic modality was developed with the aim of acting on immune cells in the tumor microenvironment - immunotherapy. The type of immunotherapy in clinical use in the treatment of head and neck tumors are immune checkpoint inhibitors, specifically inhibitors of the PD-1 (programmed death 1) signaling pathway. This paper presents an overview of tumor immunity as a basis for immunotherapy, and the specificities of the extremely immunologically active tumor microenvironment in head and neck tumors, on the basis of which the clinical application of immunotherapy in the treatment of these malignant diseases began. The issue of immunotherapy itself as a new and often still experimental therapeutic modality is elaborated; all its forms are mentioned, with special emphasis on PD-1 inhibitor therapy, which is used in head and neck tumors. Adverse events related to the use of PD-1 inhibitors, primarily adverse effects or side effects, as well as the development of resistance are also listed. Of the adverse effects, the most significant are those specific to immunotherapy; although relatively rare, they can cause serious and long-term health problems. The development of resistance represents one of the biggest problems of treatment with immunologically active compounds; the possible causes of this phenomenon are numerous, and can be found both in the nature of the tumor tissue and in the physiology of the patients themselves. In order to overcome the mentioned shortcomings of the use of immunotherapy, combinations with other therapeutic modalities common for the treatment of malignant diseases are extensively researched; some of them are already being implemented, while others are only in the early stages of testing.
Keywords
imunoterapija
tumor glave
tumor vrata
Keywords (english)
immunotherapy
head tumor
neck tumor
Language croatian URN:NBN urn:nbn:hr:105:295095 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-10-20 11:33:39
