Redundant processes in immunotherapy signaling processes revealed
Immunotherapy shows spectacular success in treating some types of cancers, but unfortunately only in a minority of patients. A study by the Gstaiger (IMSB), Aebersold (IMSB), and Malissen (CNRS Marseille) groups, which appeared in Cell Reports, identifies new redundancy mechanisms using proteomics and mouse models.
T cells can eliminate tumor cells and immunotherapy has become the newest pillar in cancer therapy. Cancer cells can however escape this killing by expressing ligands that activate inhibitory receptors (PD-1 and BTLA) on T cells, thus effectively disarming the T cells. Blocking the interaction between the tumor cell and PD-1 receptors led to spectacular therapy successes, but only in a subset of patients. In the published study, the Malissen (CNRS Marseille), Gstaiger and Aebersold (IMSB, ETH Zurich) labs used engineered mouse models and sensitive mass spectrometry-based proteomic measurements to investigate how PD-1 and BTLA receptors transmit their signals into T cells. They found molecular redundancy between these two receptors in their preference for two key signaling proteins, the tyrosyl-phosphatases SHP-1 and SHP-2 and showed that the phosphatases can substitute for each other to enable PD-1 signaling. These results open new opportunities to interfere with the molecular mechanisms by which cancer cells protect themselves from attacking T cells.
Link to the publication in external page Cell Reports.