Immunotherapy in cancer

Immunotherapy has revolutionized the treatment of cancer. However, therapy resistance and immune mediated side effects reduce the overall success. Recent developments in these two areas were reported at the 2024 ATT conference. Here we discuss that immunotherapy resistance relies on immune escape mechanisms of cancer cells. Malignant conversion of a cell encompasses oncogene activation causing altered intracellular signal transduction termed “oncogenic signaling”. A functional connection between oncogenic signaling and immune evasion mechanisms was shown for different haematological malignancies such as the FLT3-ITD/ATF6/IL-15 inhibition axis in acute myeloid leukemia. A second clinical problem are Immune mediated side effects after cancer immunotherapy because they lead to treatment interruption and potentially loss of activity by introduction of immunosuppressive medication. Anti-PD-1 immunotherapy induced inflammation of the central nervous system is rare but has a high morbidity and mortality. Recent data show that spleen tyrosine kinase (Syk) activation and downstream signaling in microglia mediates anti-PD-1 immunotherapy induced inflammation of the central nervous system.