Makrofāgu funkcionālā programmēšana vēža šūnu sferoīdu klātbūtnē
Date
2022
Authors
Korotkaja, Ksenija
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Audzēju makrofāgu (tumor-associated macrophages, TAM) pārprogrammēšana ir daudzsološa vēža imūnterapijas stratēģija. Maģistra darba ietvaros tika izveidots un raksturots jauns in vitro 3D modelis makrofāgu programmēšanas pētījumiem vēža sferoīdu klātbūtnē. Pirmkārt, tika parādīts, ka 3D kultivētajiem makrofāgiem citokīnu, hemokīnu un virsmas marķieru profils būtiski neatšķiras no monoslānī kultivētajiem makrofāgiem. Otrkārt, tika izpētītas makrofāgu pārprogrammēšanas iespējas 3D apstākļos. Iegūtie dati liecina, ka pārprogrammēšanas rezultātā tiek iegūts jaukts makrofāgu fenotips, kas ekspresē gan imūnsupresīvus, gan pretvēža imūnstimulējošus faktorus. Treškārt, tika parādīts, ka vēža šūnu sferoīds stimulē imūnsupresīvo marķieru, kā arī citokīnu un hemokīnu profilu veidošanos makrofāgu programmēšanas un pārprogrammēšanas laikā.
The reprogramming of tumor-associated macrophages (TAMs) is a promising cancer immunotherapy strategy. A new in vitro 3D model for the research of macrophage programming in the presence of cancer spheroids was developed and described as part of the master's thesis. First, it was demonstrated that the cytokine, chemokine, and surface marker profiles of 3D cultured macrophages did not differ significantly from those of monolayer cultured macrophages. Second, the possibilities of 3D macrophage reprogramming were investigated. According to the findings, reprogramming results in a mixed macrophage phenotype that expresses both immunosuppressive and anti-cancer immunostimulatory factors. Third, during macrophage programming and reprogramming, cancer cell spheroids have been shown to stimulate the expression of immunosuppressive markers as well as cytokine and chemokine profiles.
The reprogramming of tumor-associated macrophages (TAMs) is a promising cancer immunotherapy strategy. A new in vitro 3D model for the research of macrophage programming in the presence of cancer spheroids was developed and described as part of the master's thesis. First, it was demonstrated that the cytokine, chemokine, and surface marker profiles of 3D cultured macrophages did not differ significantly from those of monolayer cultured macrophages. Second, the possibilities of 3D macrophage reprogramming were investigated. According to the findings, reprogramming results in a mixed macrophage phenotype that expresses both immunosuppressive and anti-cancer immunostimulatory factors. Third, during macrophage programming and reprogramming, cancer cell spheroids have been shown to stimulate the expression of immunosuppressive markers as well as cytokine and chemokine profiles.
Description
Keywords
Bioloģija , audzēju makrofāgi , makrofāgu pārprogrammēšana , 3D in vitro modeļi , vēža šūnu sferoīdi