Immunology and Immunotherapy of Solid Tumors (Noessner)

Department / Institute
Immunoanalytics – Tissue Control of Immunocytes (IMA-TCI), Department “Molecular Targets & Therapeutics Center” (MTTC), Helmholtz Zentrum München
Subject area
Immunology and Immunotherapy of Solid Tumors
Project title
The role of macrophages in the regulation of antitumor immunity and therapy resistance
Name of supervisor
Prof. Dr. rer. nat. Elfriede Noessner
Number of open positions
Language requirements
Proficiency in English
Academic requirements
Master's Degree
Project time plan
Full Doctoral Study-Model: 36 or 48 months

Project description

Checkpoint inhibition is meanwhile an established treatment strategy for many tumor entities by which the inhibitory signal between PD-1 and PD-L1 is prevented through monoclonal antibodies binding to either PD-1 or PD-L1 (Mantia & McDermott, 2019). Response rates of this clinical application vary (Ribas & Wolchok, 2018), and more than half of patients do not respond. The reason why many patients to not respond is an area of intense debate and research. In our group, we have analyzed the tumor milieu of renal cell carcinoma (RCC) for many years. We have identified dysfunction in T and NK cells (Prinz et al. 2012, 2014) as well as uniquely polarized macrophages in RCC tissue (Figel et al. 2011; Brech et al. 2020). Therefore, we rationally proposed an inhibitory role of macrophages on T cell function (Noessner et al. 2012), and hypothesize that the presence of macrophages will prevent checkpoint inhibition from being fully active in RCC. A recent study has revealed an enrichment of exhausted CD8+ T cells together with immunosuppressive macrophages associated with immune dysfunction in advanced RCC tissues (Braun et al. 2021). Therapeutic targeting of macrophages should be the next required step to increase the number of patients that can benefit from checkpoint inhibition therapy. Another concern in the field is that the immune profile of primary tumor and metastasis might be different. Metastasis is the cause of disease progression. If the immune profile of the metastasis would be different to that of the primary tumor, an issue that is currently unsolved, any therapy selected based on the immune profile of the primary tumor may not be active against metastasis and may not offer survival benefit to patients.

The project aims are: 1) Deep profiling of the macrophages in human carcinomas and identification of therapeutic targets for functional repolarization. 2) Characterizing the immune composition of primary RCC tumors and corresponding metastasis of RCC.

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