From Priming to Therapy: Leveraging New Insights in T Cell Activation

CD8 T cells constitute one of the pillars of the adaptive immune response. They play a key role in eliminating pathogen-infected and cancerous cells. To effectively carry out their function, naïve CD8 T cells must undergo priming/activation in which several cell types, receptors, cytokines, and chemokines are involved. Various therapeutic approaches, such as vaccinations and anti-cancer therapies, i.e., immune checkpoint blockade (ICB) and Chimeric Antigen Receptor (CAR) T cell transfer, attempt to harness CD8 T cell biology to protect from or treat life-threatening diseases. Despite the significant success of CD8-T-cell-related therapies, the overall response rate of cancer patients remains relatively low, perhaps due to an incomplete understanding of the crucial events leading to optimal CD8 T cell activation. Recent findings highlight the importance of CD4 T cell help in CD8 T cell priming as well as the existence of an additional priming phase for the selection and expansion of high affinity T cells. Together, these findings offer a refined conceptual framework to guide future research and therapeutic development. Here, we present a revised perspective on clinically relevant CD8 T cell–based therapies in light of recent discoveries.