Evaluating Immunoediting and Clonal Dynamics in Smoldering Myeloma Progression

Cancer immunoediting is a complex process where the immune system can either restrain or promote tumour development. Myeloma, a prevalent incurable blood cancer, provides an ideal model for exploring this concept during disease evolution, as it is preceded by smouldering myeloma. If mutations have been associated with the transition from smouldering to myeloma, the role of immune changes observed remains undetermined. Further evidence suggests that mechanisms of progression are subtype-specific with notable differences observed within the most prevalent subtypes, the standard-risk groups. The hypothesis underlying this study is that the interplay between the host immune response and the tumour characteristics determines smouldering homeostasis in a subtype-specific manner. To test this, I will analyse tumour and microenvironment interactions in standard-risk smouldering patients. I will assess tumour homeostasis, immunoediting, and the impact of genetic subtypes on disease progression using a combination of sequencing and in vitro assays. These data will reveal how the immune microenvironment affects tumour quality, identify subgroup-specific progression factors, and guide clinical interventions at the smouldering stage. Ultimately, this research could extend to other cancers and provide insights into the role of immunoediting in tumour progression.