IL-17 u ranom invazivnom raku dojke

doctoral thesis

• Title (english): IL-17 in early invasive breast cancer
• Author: Marina Popović
• Mentor: Natalija Dedić Plavetić (mentor)
• Mentor: Ana Kulić (komentor)
• Committee member: Stjepko Pleština (predsjednik povjerenstva)
• Committee member: Drago Batinić (član povjerenstva)
• Committee member: Jasminka Jakić-Razumović (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2022-09-22, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Interleukin 17 (IL-17) je središnji medijator upale s višestrukom ulogom u nastanku,
napredovanju i rezistenciji na terapiju tumora različitih sijela. Pojedine studije govore u prilog
antitumorske aktivnosti IL-17 dok je prema drugima nađeno da povećana izraženost IL-17 u
tumorskom tkivu dojke doprinosi agresivnosti tumora i lošijoj prognozi. Uloga IL-17 dosad je
većinom ispitivana na in vitro staničnim modelima i ljudskim ksenograftima. Nedostatak
podataka o učincima IL-17 in vivo predstavlja nepremostivu prepreku u terapijskom
moduliranju IL-17 posredovanih imunoloških reakcija radi uspješnijeg liječenja bolesnika
oboljelih od raka. U ovom istraživanju analizirana je koncentracija IL-17 u serumu 118 žena
oboljelih od ranog invazivnog raka dojke prije operacije i tijekom adjuvantnog liječenja i
uspoređena s koncentracijom IL-17 u serumu kontrolne skupine zdravih žena. Analizirana je
razina izraženosti IL-17 u različitim komponentama pridruženih intraoperativnih uzoraka
bolesnica uključujući invazivnu i in situ komponentu, peritumorsku stromu i normalno tkivo
dojke. Utvrđena je značajno viša serumska koncentracija IL-17 u serumu žena oboljelih od
ranog raka dojke prije početka liječenja (P<0,001), ali i nakon kirurškog odstranjenja tumora
tijekom adjuvantnog liječenja u odnosu na kontrolnu skupinu (P=0,001) koja nije značajno
korelirala s izražajem IL-17 u tumorskom tkivu. Nađen je statistički značajan pad razine
IL-17 u serumu žena oboljelih od ranog raka dojke tijekom adjuvantnog liječenja nakon
operacije u odnosu na vrijednosti prije operacije (P<0,001). Razina IL-17 u serumu bolesnica
oboljelih od ranog raka dojke značajno je negativno korelirala s izražajem estrogenskih
receptora u tumoru. Rezultati govore u prilog tome da je imunološki odgovor u ranom raku
dojke, među ostalim, posredovan i stanicama koje luče IL-17, osobito u trostruko negativnom
raku dojke. Utvrđeno je da po odstranjenju tumora dolazi do smirivanja upalne reakcije
posredovane IL-17, ali se razina IL-17 nakon odstranjenja tumora tijekom adjuvantnog
liječenja ne vraća na normalne vrijednosti već ostaje povišena u odnosu na vrijednosti u
zdravoj populaciji.

Abstract (english)

Interleukin 17 (IL-17) has a key role in inflammatory responses. Increased levels of
IL-17 have been reported in the serum of cancer patients. Some studies suggest antitumor
activity of IL-17 and others speak in favor of its association with poorer prognosis. The lack
of data on IL-17 behavior in vivo precludes the usage of IL-17 antibodies in cancer patients.
This study included 118 patients with early invasive breast cancer. The serum concentration
of IL-17 was measured before surgery and during adjuvant treatment and compared with
healthy controls. The level of IL-17 expression in the corresponding tumor tissue samples was
analyzed. Significantly higher serum concentrations of IL-17 were found in the serum of
women with early breast cancer before treatment and during adjuvant treatment without
correlation to tumor tissue IL-17 expression. There was a significant decrease in serum IL-17
levels in women with early breast cancer after surgery compared to preoperative values.
Serum IL-17 levels were significantly negatively correlated with tumor estrogen receptor
expression. The results suggest that the immune response in early breast cancer is mediated
also by IL-17, particularly in triple-negative breast cancer. IL-17-mediated inflammatory
response subsided after tumor removal, but IL-17 levels remained elevated compared to
healthy controls.

• Keywords: Interleukin-17; Receptori; estrogen; Trostruko negativne neoplazme dojke; Prognoza; Imunitet
• Keywords (english): Interleukin-17; Receptors; Estrogen; Triple Negative Breast Neoplasms; Prognosis; Immunity
• Language: croatian
• URN:NBN: urn:nbn:hr:105:271798
• Project: Number: 108-1080058-0046; Title: KARCINOM DOJKE-MOLEKULARNE,GENETSKE I KLINIČKE KARAKTERISTIKE; Title: BREAST CANCER-MOLECULAR, GENETIC AND CLINICAL CHARACTERISTICS; Leader: Damir Vrbanec; Jurisdiction: Croatia; Funder: MZOS; Funding stream: ZP
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 100 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-10-25 07:00:29