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

Abstract

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.

Keywords

CD8 T cells / CD4 helper cells / Priming / Therapy

Author Contributions

Writing—Review & Editing: K.J., D.S. and W.K.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Funding

W.K. is supported by the Max Planck Society (Max Planck Research Groups), the German Research Foundation (DFG) (CRC/TRR 338 Nr. 452881907 and CRC1583 Nr. 492620490) and the European Research Council (ERC) W.K.(819329-STEP2).

Declaration of Competing Interest

The authors declare that they have no competing interests.

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