SFB 1335: Aberrant Immune Signals in Cancer

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The immune system has a pivotal role in cancer pathogenesis and biology, as well as in tumour therapy. Its unique ability to recognize cancer cells of various histological origins and to orchestrate protective immune responses for efficient tumour cell killing has been successfully harnessed for cancer immunotherapy, which dramatically advanced the prognosis of individual cancer patients. However, antitumour immune responses are frequently impaired or only short-lived. Furthermore, pathological immune signals in the microenvironment of cancer cells can even directly promote malignancy and actively subvert tumour immune surveillance. Furthermore, immune cells themselves can also be targets of malignant transformation, and leukaemia or lymphoma are frequently triggered by oncogenic mutations which affect immune receptor signalling modules. Collectively, we consider the pathological signals that originate within, or are mediated by immune cells, and which ultimately support or promote malignancy, as aberrant immune signals in cancer. Our interdisciplinary network of clinical and basic scientists with key expertise in immunology and oncology, explore how corrupted immune signals trigger the development of haematopoietic malignancies, drive tumour-promoting inflammation or mediate evasion from antitumour immunity. To this end, we focus on model malignancies of the haematopoietic system, gastrointestinal tract and skin, in scenarios where a link between deviated immune signalling and neoplastic growth has been established in clinical settings. Using relevant mouse models of human disease and patient-derived material, together with novel enabling technologies including advanced molecular and cellular immunology and tumour biology methods, genetic engineering, organoids and in vivo screening, as well as microbiome, metabolome and high-dimensional single-cell and spatio-molecular histopathological analyses, we aim to generate new knowledge that will ultimately lead to the design of novel strategies to target aberrant immune signals for better anti-cancer therapies.