TY  - JOUR
A1  - Brosinsky, Paulin
A1  - Leister, Hanna
A1  - Cheng, Nan
A1  - Varelas, Xaralabos
A1  - Visekruna, Alexander
A1  - Luu, Maik
T1  - Verteporfin protects against Th17 cell‐mediated EAE independently of YAP inhibition
JF  - European Journal of Immunology
N2  - The known YAP inhibitor verteporfin is capable of repressing IL‐17A production in Th17 cells. However, this effect is mediated independently of YAP and can ameliorate Th17‐mediated experimental autoimmune encephalomyelitis (EAE) upon in vivo administration. The data suggest verteprofin's mode of action for the design of novel therapeutic autoimmune disease intervention.
KW  - Hippo signaling
KW  - YAP
KW  - verteporfin
KW  - Th17 cells
KW  - EAE
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287234
VL  - 52
IS  - 9
SP  - 1523
EP  - 1526
ER  - 
TY  - JOUR
A1  - Luu, Maik
A1  - Schütz, Burkhard
A1  - Lauth, Matthias
A1  - Visekruna, Alexander
T1  - The impact of gut microbiota-derived metabolites on the tumor immune microenvironment
JF  - Cancers
N2  - Prevention of the effectiveness of anti-tumor immune responses is one of the canonical cancer hallmarks. The competition for crucial nutrients within the tumor microenvironment (TME) between cancer cells and immune cells creates a complex interplay characterized by metabolic deprivation. Extensive efforts have recently been made to understand better the dynamic interactions between cancer cells and surrounding immune cells. Paradoxically, both cancer cells and activated T cells are metabolically dependent on glycolysis, even in the presence of oxygen, a metabolic process known as the Warburg effect. The intestinal microbial community delivers various types of small molecules that can potentially augment the functional capabilities of the host immune system. Currently, several studies are trying to explore the complex functional relationship between the metabolites secreted by the human microbiome and anti-tumor immunity. Recently, it has been shown that a diverse array of commensal bacteria synthetizes bioactive molecules that enhance the efficacy of cancer immunotherapy, including immune checkpoint inhibitor (ICI) treatment and adoptive cell therapy with chimeric antigen receptor (CAR) T cells. In this review, we highlight the importance of commensal bacteria, particularly of the gut microbiota-derived metabolites that are capable of shaping metabolic, transcriptional and epigenetic processes within the TME in a therapeutically meaningful way.
KW  - tumor microenvironment (TME)
KW  - commensal bacteria
KW  - intratumoral microbiota
KW  - oncobiome
KW  - microbiota-derived metabolites
KW  - cancer immunotherapy
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311005
SN  - 2072-6694
VL  - 15
IS  - 5
ER  - 
TY  - JOUR
A1  - Staudt, Sarah
A1  - Ziegler-Martin, Kai
A1  - Visekruna, Alexander
A1  - Slingerland, John
A1  - Shouval, Roni
A1  - Hudecek, Michael
A1  - Van den Brink, Marcel
A1  - Luu, Maik
T1  - Learning from the microbes: exploiting the microbiome to enforce T cell immunotherapy
JF  - Frontiers in Immunology
N2  - The opportunities genetic engineering has created in the field of adoptive cellular therapy for cancer are accelerating the development of novel treatment strategies using chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. The great success in the context of hematologic malignancies has made especially CAR T cell therapy a promising approach capable of achieving long-lasting remission. However, the causalities involved in mediating resistance to treatment or relapse are still barely investigated. Research on T cell exhaustion and dysfunction has drawn attention to host-derived factors that define both the immune and tumor microenvironment (TME) crucially influencing efficacy and toxicity of cellular immunotherapy. The microbiome, as one of the most complex host factors, has become a central topic of investigations due to its ability to impact on health and disease. Recent findings support the hypothesis that commensal bacteria and particularly microbiota-derived metabolites educate and modulate host immunity and TME, thereby contributing to the response to cancer immunotherapy. Hence, the composition of microbial strains as well as their soluble messengers are considered to have predictive value regarding CAR T cell efficacy and toxicity. The diversity of mechanisms underlying both beneficial and detrimental effects of microbiota comprise various epigenetic, metabolic and signaling-related pathways that have the potential to be exploited for the improvement of CAR T cell function. In this review, we will discuss the recent findings in the field of microbiome-cancer interaction, especially with respect to new trajectories that commensal factors can offer to advance cellular immunotherapy.
KW  - microbiome
KW  - immunotherapy
KW  - immunology
KW  - cancer immune cell therapy
KW  - CAR T cell
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-328019
VL  - 14
ER  -