The Role of Ribosomal Heterogeneity in T Cell Recognition of Tumor Cells

ASPIRE Award (2021-Present)

Pia Kvistborg, PhD and William Faller, PhD, Netherlands Cancer Institute (NKI) (The Netherlands)

Immunotherapy has shifted the paradigm of treating cancer by enhancing the immune system’s ability to recognize cancer cells as foreign. Unfortunately, immunotherapy is only fully effective for a minority of cancer patients. This underscores the need for a better understanding of the processes that underlie T cell recognition and elimination of tumor cells, and the development of novel biomarkers and therapies.

Tumor surveillance by T cells is essential for immunotherapy and depends on the presentation of antigens on the tumor cell surface. Recent studies have shown that ribosomes, historically thought of as an unchanging passive mediators of RNA translation, are actually structurally and functionally heterogeneous, and evidence suggests that certain ribosomal proteins influence T cell recognition of tumor cells.

With this ASPIRE Award, Kvistborg’s group will identify which ribosomal proteins can influence T cell recognition of tumors, what changes in the translational landscape are caused by those ribosomal proteins, and how those changes impact the pool of antigens available for cell surface presentation. These studies will reframe our understanding of how translation and ribosomal heterogeneity influence the drivers of tumor-specific immune responses and how to increase the visibility of tumors to T cells.