SOFIA CAVADA

Rhabdoid tumors (RTs) are aggressive pediatric cancers that manifest in various organs, such as the liver, kidney, and brain. These tumors exhibit one of the lowest mutational burdens observed in cancer, primarily driven by the bi-allelic inactivation of SMARCB1, leading to alterations in the SWI/SNF chromatin remodeler complex (Versteege et al., 1998; Lee et al., 2012). Due to their low mutational burden and genetic similarity to self, RTs were long assumed to be invisible to the immune system, making them poor candidates for immunotherapy (Rizvi et al., 2015). Consequently, their treatment typically involves intensive measures such as surgery, chemotherapy, and radiotherapy, which are effective in only a minority of children and often result in severe sequelae and high relapse rates.

Recent research conducted by the team at Institut Curie has challenged this assumption. Studies using human RT samples and a unique RT mouse model (Han et al., 2016) revealed that RTs are highly infiltrated by clonally expanded CD8+ T cells and myeloid cells. In my project the focus is mainly on this second group of myeloid cells, particularly on neutrophils—immune cells that for many years were regarded as a homogeneous, terminally differentiated population with limited functional versatility. However, recent research has overturned this view, revealing that neutrophils encompass a broad spectrum of phenotypes and activities. In the context of cancer, they have been implicated in both anti-tumor and pro-tumor roles, influencing processes such as tumor progression, immune evasion, metastasis, and relapse. This duality is thought to arise from their remarkable plasticity, shaped by tumor-derived signals and the surrounding microenvironment, positioning them as key modulators of cancer biology and potential targets for therapeutic intervention.