Dynamics of T lymphocyte responses following vaccination

The adaptive immune responses mediated by T lymphocytes play a critical role in host protection against pathogens and malignant tumors. Following activation by antigens, naïve T lymphocytes establish specific heritable gene expression programs that guides the progression to long-lasting memory or short-lived effector subsets. Understanding the lineage relationships between naïve, effectors and memory T cells, and the molecular pathways that regulate gene expression during the transitions between these distinct states, is essential for the rational design of vaccines and development of new immune-therapeutic protocols.

In the context of cancer, we show, by single-cell multi-omics, that adenovirus (Ad) vaccine targeting tumor neoepitopes enhances anti-tumor efficacy, by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors. The translational relevance of these data is supported by results obtained in the first metastatic patients treated with an Ad vaccine encoding tumor neoantigens.

We have also recently examined CD8 + T cell heterogeneity during the different stages of T cell differentiation, by developing an integrative approach at the single-cell level. These results establish a transcriptional “map” during CD8+ T cell lineage commitment, highlighting new interclonal relationships between different CD8+ T subsets, during the different stages of differentiation.

Recent results and new perspectives will be discussed in the context of long-term memory and T cell-based cancer immunotherapies.