The effect of tertiary lymphoid structures on cancer immunotherapy response

Recent breakthroughs in the management of melanomas take advantage of the power of the immune system to achieve previously unattainable control of the disease.

However, there is a growing appreciation of the limitation of current immunotherapies, reflected in both primary and acquired resistance to treatment.

To overcome therapy-resistance we need more knowledge on how the immunotherapy affects the tumor, the surrounding stroma and the anti-tumor immune response.

The novelty of our proposed work lies in the utility of state-of the art spatial genomic technologies applied on unique patient tissue in combination with excellent model systems that will provide groundbreaking mechanistic insights.

This work will for the first time uncover cellular subsets and molecular details of immune cell niches present in human melanoma metastases.

Moreover, using patient derived organoid and ex vivomodels we will decipher activated signaling networks conferred by TLSs or immune cell niches during immunotherapy treatment.

Using sophisticated mouse models we will further unravel the impact of B cells acting as antigen presenting cells in the context of TLSs and immunotherapy.

Consequently, our work will provide groundbreaking insights in the role of immune cell niches and TLSs in the anti-tumor immune response in melanoma.