Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kienzl, M; Hasenoehrl, C; Maitz, K; Sarsembayeva, A; Taschler, U; Valadez-Cosmes, P; Kindler, O; Ristic, D; Raftopoulou, S; Santiso, A; Bärnthaler, T; Brcic, L; Hahnefeld, L; Gurke, R; Thomas, D; Geisslinger, G; Kargl, J; Schicho, R.
Monoacylglycerol lipase deficiency in the tumor microenvironment slows tumor growth in non-small cell lung cancer.
Oncoimmunology. 2021; 10(1): 1965319
Doi: 10.1080/2162402X.2021.1965319
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- Führende Autor*innen der Med Uni Graz
- Kargl Julia
- Kienzl Melanie
- Co-Autor*innen der Med Uni Graz
- Bärnthaler Thomas
- Brcic Luka
- Hasenöhrl Carina
- Kindler Oliver
- Maitz Kathrin
- Raftopoulou Sofia
- Ristic Dusica
- Santiso Sanchez Ana Luisa
- Sarsembayeva Arailym
- Schicho Rudolf
- Taschler Ulrike
- Valadez Cosmes Paulina
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- Abstract:
- Monoacylglycerol lipase (MGL) expressed in cancer cells influences cancer pathogenesis but the role of MGL in the tumor microenvironment (TME) is less known. Using a syngeneic tumor model with KP cells (KrasLSL-G12D/p53fl/fl; from mouse lung adenocarcinoma), we investigated whether TME-expressed MGL plays a role in tumor growth of non-small cell lung cancer (NSCLC). In sections of human and experimental NSCLC, MGL was found in tumor cells and various cells of the TME including macrophages and stromal cells. Mice treated with the MGL inhibitor JZL184 as well as MGL knock-out (KO) mice exhibited a lower tumor burden than the controls. The reduction in tumor growth was accompanied by an increased number of CD8+ T cells and eosinophils. Naïve CD8+ T cells showed a shift toward more effector cells in MGL KOs and an increased expression of granzyme-B and interferon-γ, indicative of enhanced tumoricidal activity. 2-arachidonoyl glycerol (2-AG) was increased in tumors of MGL KO mice, and dose-dependently induced differentiation and migration of CD8+ T cells as well as migration and activation of eosinophils in vitro. Our results suggest that next to cancer cell-derived MGL, TME cells expressing MGL are responsible for maintaining a pro-tumorigenic environment in tumors of NSCLC.
- Find related publications in this database (Keywords)
- Endocannabinoid
- 2-AG
- cannabinoid receptors
- lung cancer
- monoacylglycerol lipase
- immune cells
- CD8(+) T cells