Cancers take advantage of the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) to promote an immunosuppressive microenvironment and to enhance tumor cell motility. We have developed a unique AHR signature, which can detect AHR activity and AHR-mediated biological functions irrespective of tissue and ligand. In cancer, the AHR likely represents a resistance mechanism against therapies that activate the immune system, including radiation, chemotherapy and immunotherapies, because immune activation further enhances AHR activity, which in turn suppresses immune responses. Moreover, AHR expression and activity are modulated by tyrosine kinase inhibition. We will therefore analyze AHR activity as a predictor of the efficacy of tyrosine kinase inhibition, radio/chemotherapy, and immune therapies. We will analyze samples from malignant melanoma, glioma, sarcoma, lung cancer and chronic lymphocytic leukemia from clinical trials of the German Cancer Consortium. In summary, PredictAHR will investigate the predictive power of the AHR signature in different cancer types and develop assays for AHR activity that can be integrated into the clinics.