Research Topic

New Horizons in Tumor Microenvironment Biology and Therapy: Implications for New Therapies

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The tumor microenvironment (TME) is heterogenous and poses enormeous therapeutic potential as recently proven by the therapeutic success of antibodies inducing immune cell stimulation (e.g. immune checkpoint inhibitors) and anti-angiogenic therapies (e.g. targeting VEGF/VEGFR signaling). The interplay between ...

The tumor microenvironment (TME) is heterogenous and poses enormeous therapeutic potential as recently proven by the therapeutic success of antibodies inducing immune cell stimulation (e.g. immune checkpoint inhibitors) and anti-angiogenic therapies (e.g. targeting VEGF/VEGFR signaling). The interplay between the TME and the cancer cell compartment is essential for therapeutic efficacy of many anti-cancer agents; however, the dynamics and the complexity of this network is not yet well characterized. Recent studies highlighting the complex interactions of the various TME components demonstrated, for example, that immune checkpoint inhibitors induce vascular changes and, that vice versa anti-angiogenic therapies may help to reverse immune exhaustion.

The aim of this Research Topic is to summarize the recent advances in the characterization of the TME focusing on techniqual advances (genetic advances as single cell technologies and immuno-genetics) that led to a better understanding of the complex regulation of the TME, and how therapeutic strategies that focus on the inhibition of the TME could be complementary with standard therapies. Essential for understanding the TME is also to model the TME in ex vivo 3D culture systems and how this orgnaoid can be used for drug testing. Furthermore, the vascular network is an essential regulator and key player of the TME and therefore we will highlight how tumor endothelial cells rewire their phenotype, including their metabolism for interaction with the immune system and vice versa (barrier function of ECs in the brain, gut vascular barrier and microbiome interaction, colorectal cancer TME).

Next we would aim to report on metabolic changes during metastasis formation and how cancer cells have to adapt to their new environment. Recently, metabolic investigations led to the identification of metabolic symbiosis of cancer cells and the TME compartment. This metabolic features pose therapeutic potential and might me synergistic with standard therapies.

Finally, particular emphasis will be placed on the understanding of sterile inflammation pathways (e.g. nuleic acid sensing) in the TME and the TME inflammation-mediated cancer cell plasticity. As an outlook, those TME aspects will set into a clinical context by discussing the TME of high immunogenic and angiogenic dependet tumors (as prototype renal cell cancer (RCC), myeloproliferative neoplasms (MPN) and the interation of the bone marrow with the vascular niche in acute myeloid leukemia (AML)) to exemplify also potential synergies the TME-targeting therapies.

In summary, this Research Topic will give a state of the art update on new biological and technical advances in the composition of the TME focusing on the vascular network and interaction with tumor immunology and how this knowledge could translate to new therapeutic strategies.


Keywords: Tumor angiogenesis, immune cell infiltration, tumor microenviroment, compartimentailzation, new targets


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