Uloga i značenje proteina toplinskog šoka u anti-tumorskoj imunosti

undergraduate thesis

• Title (english): The role and significance of heat shock proteins in anti-tumor immunity
• Author: Lucija Jelaska
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-20, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Proteini toplinskog šoka prisutni su u svim stanicama i neophodni su za njihovo preživljavanje.
Indukciju ekspresije gena za HSP potiču stresni uvjeti od kojih je najvažniji toplinski šok. Zaštitna
uloga u stanicama olakšava preživljavanje i progresiju tumora štiteći takve promijenjene stanice
od smrti. Kada dođe do ispuštanja HSP iz stanice tijekom nekroze ili vezikulama takvi šaperoni
dobivaju i novu ulogu pokretača anti-tumorske imunosti. Vežući se samostalno na receptore
makrofaga preuzimaju ulogu signala opasnosti i pokreću upalni odgovor i aktivaciju makrofaga
koji proždiru tumorske stanice. Oslobođeni HSP-ovi mogu se povezivati u komplekse s drugim
ispuštenim tumorskim antigenima i kao takvi olakšavaju njihov unos u antigen-predočne stanice.
Dendritične stanice antigene unesene u sklopu takvih komplekasa prerađuju i izlažu na površini
MHC-I molekulama naivnim CD8+ stanicama T. Tim procesom križnog predočavanja započinje
adaptivni imunosni odgovor koji uključuje citotoksično djelovanje T-stanica. Mehanizam kojim
CTL razaraju tumorske stanice ovisan je o HSP70 vezanim za membranu ciljne stanice koji
pospješuje ulaz proapoptotskog ispuštenog enzima granzima B. HSP vezan za membranu
omogućuje prirodnoubilačkim stanicama ubijanje tumorskih stanica koje su izbjegle napad stanica
T i time poboljšava ukupni protutumorski odgovor.

Abstract (english)

Heat shock proteins exist in all cells and are necessary for their survival. The induction of HSP
gene expression is triggered in stressful conditions, with heat shock being the most important one.
Their protective role in cells facilitates survival and tumor progression by protecting these altered
cells from death. When HSP is released from the cell during necrosis or by vesicles, these
chaperones take on a new role as drivers of anti-tumor immunity. By binding independently to
macrophage receptors, they take on the role of danger signals and initiate an inflammatory response
and macrophage activation, which leads to the capture and destruction of tumor cells. Released
HSPs can also form complexes with other released tumor antigens, facilitating their uptake by
antigen-presenting cells. Dendritic cells process the antigens taken up within these complexes and
present them with MHC-I molecules to naïve CD8+ T cells. This process of cross-presentation
initiates an adaptive immune response, including the cytotoxic actions of T cells. The mechanism
by which CTLs destroy tumor cells depends on membrane-bound HSP70 on the target cell, which
enhances the entry of the pro-apoptotic enzyme granzyme B. Membrane-bound HSP also enables
natural killer cells to kill tumor cells that have evaded T cell attack, thereby enhancing the overall
anti-tumor response.

• Keywords: eHSP; križno predočavanje; CTL; granzim B
• Keywords (english): eHSP; cross-presentation; CTL; granzyme B
• Language: croatian
• URN:NBN: urn:nbn:hr:217:880945
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-09-26 12:40:08