<p>Immunotherapies offer promising new therapeutic avenues in oncology. However, as both primary resistance (existing before the start of therapy) and acquired resistance induced by therapy can occur, not all patients benefit from these immunotherapy options. Even in types of cancer for which checkpoint inhibitors, for example, are standard therapy, there is a&#xa0;significant proportion of patients who do not benefit from this immunotherapy. Resistance mechanisms utilize many regulatory mechanisms (simultaneously). Possible resistance mechanisms can, for example, prevent the immune system from recognizing the tumor. The reduced synthesis and expression of major histocompatibility complex (MHC) molecules and the reduced or complete lack of processing and presentation of tumor antigens are of great importance here. Impairment of the antitumor effect of immune cells, e.g., by inducing the exhaustion of T&#xa0;cells and changes in the tumor microenvironment such as barrier formation, can also contribute to resistance to immunotherapies. In this ensemble of possible resistance mechanisms, differences between the tumor entities and the organ systems involved are also important. Together, this creates a&#xa0;complex landscape of altered (molecular) regulatory circuits that can counteract the effect of immunotherapy in individual patients. The challenge for the future here is to recognize these altered regulatory circuits and to identify them in the individual patient.</p>