SFB 1335: Aberrant Immune Signals in Cancer

免疫系统在癌症发病机制和生物学以及肿瘤治疗中具有关键作用。它识别各种组织学来源的癌细胞并协调保护性免疫反应以有效杀死肿瘤细胞的独特能力已成功用于癌症免疫治疗，这大大提高了个体癌症患者的预后。然而，抗肿瘤免疫应答经常受损或仅短暂存在。此外，癌细胞微环境中的病理性免疫信号甚至可以直接促进恶性肿瘤的发生，并主动破坏肿瘤的免疫监视。此外，免疫细胞本身也可能是恶性转化的靶点，白血病或淋巴瘤通常由影响免疫受体信号传导模块的致癌突变引发。总的来说，我们认为起源于免疫细胞内或由免疫细胞介导的病理信号，最终支持或促进恶性肿瘤，作为癌症中的异常免疫信号。我们的跨学科临床和基础科学家网络具有免疫学和肿瘤学的关键专业知识，探索受损的免疫信号如何触发造血系统恶性肿瘤的发展，驱动肿瘤促进炎症或介导抗肿瘤免疫的逃避。为此，我们专注于造血系统，胃肠道和皮肤的模型恶性肿瘤，在偏离免疫信号和肿瘤生长之间的联系已经在临床环境中建立的情况下。利用人类疾病的相关小鼠模型和患者源性材料，以及新的赋能技术，包括先进的分子和细胞免疫学和肿瘤生物学方法、基因工程、类器官和体内筛选，以及微生物组、代谢组和高维单细胞和空间分子组织病理学分析，我们的目标是产生新的知识，最终导致设计新的策略，以靶向异常的免疫信号，以获得更好的抗癌疗法。

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.