Oncogenic MYD88 mutations in lymphoma: novel insights and therapeutic possibilities

AbstractOncogenicMYD88 mutations, most notably the Leu 265 Pro (L265P) mutation, were recently identified as potential driver mutations in various B-cell non-Hodgkin Lymphomas (NHLs). The L265P mutation is now thought to be common to virtually all NHLs and occurs in between 4 and 90% of cases, depending on the entity. Since it is tumor-specific, the mutation, and the pathways it regulates, might serve as advantageous therapeutic targets for both conventional chemotherapeutic intervention, as well as immunotherapeutic strategies. Here, we review recent progress on elucidating the molecular and cellular processes affected by the  L265P mutation ofMYD88, describe a new in vivo model for MyD88 L265P-mediated oncogenesis, and summarize how these findings could be exploited therapeutically by specific targeting of signaling pathways. In addition, we summarize current and explore future possibilities for conceivable immunotherapeutic approaches, such as L265P-derived peptide vaccination, adoptive transfer of L265P-restricted T cells, and use of T-cell receptor-engineered T cells. With clinical trials regarding their efficacy rapidly expanding to NHLs, we also discuss potential combinations of immune checkpoint inhibitors with the described targeted chemotherapies of L265P signaling networks, and/or with the above immunological approaches as potential ways of targetingMYD88-mutated lymphomas in the future.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research