The proteome and transcriptome of stress granules and P bodies during human T lymphocyte activation.

Stress granules (SGs) and processing bodies (PBs) are membraneless cytoplasmic assemblies regulating mRNAs under environmental stress such as viral infections, neurological disorders, or cancer. Upon antigen stimulation, T lymphocytes mediate their immune functions under regulatory mechanisms involving SGs and PBs. However, the impact of T cell activation on such complexes in terms of formation, constitution, and relationship remains unknown. Here, by combining proteomic, transcriptomic, and immunofluorescence approaches, we simultaneously characterized the SGs and PBs from primary human T lymphocytes pre and post stimulation. The identification of the proteomes and transcriptomes of SGs and PBs indicate an unanticipated molecular and functional complementarity. Notwithstanding, these granules keep distinct spatial organizations and abilities to interact with mRNAs. This comprehensive characterization of the RNP granule proteomic and transcriptomic landscapes provides a unique resource for future investigations on SGs and PBs in T lymphocytes.

Cancer cell adaptability: turning ribonucleoprotein granules into targets.

Stress granules (SGs) and processing bodies (P-bodies) are membraneless cytoplasmic condensates of ribonucleoproteins (RNPs). They both regulate RNA fate under physiological and pathological conditions, and are thereby involved in the regulation and maintenance of cellular integrity. During tumorigenesis, cancer cells use these granules to thrive, to adapt to the harsh conditions of the tumor microenvironment (TME), and to protect themselves from anticancer treatments. This ability to provide multiple outcomes not only makes RNP granules promising targets for cancer therapy but also emphasizes the need for more knowledge about the biology of these granules to achieve clinical use. In this review we focus on the role of RNP granules in cancer, and on how their composition and regulation might be used to elaborate therapeutic strategies.

Stress Granules in the Post-transcriptional Regulation of Immune Cells.

Immune cell activation triggers transcriptional and translational programs eliciting cellular processes, such as differentiation or proliferation, essential for an efficient immune response. These dynamic processes require an intricate orchestration of regulatory mechanisms to control the precise spatiotemporal expression of proteins. Post-transcriptional regulation ensures the control of messenger RNA metabolism and appropriate translation. Among these post-transcriptional regulatory mechanisms, stress granules participate in the control of protein synthesis. Stress granules are ribonucleoprotein complexes that form upon stress, typically under control of the integrated stress response. Such structures assemble upon stimulation of immune cells where they control selective translational programs ensuring the establishment of accurate effector functions. In this review, we summarize the current knowledge about post-transcriptional regulation in immune cells and highlight the role of stress sensors and stress granules in such regulation.

Regulatory Mechanisms of Inhibitory Immune Checkpoint Receptors Expression.

T cells responding to persistent tumor or viral antigens progressively lose their functional properties, a feature known as exhaustion. This state is also characterized by cell-surface expression of multiple inhibitory immune checkpoint receptors (IRs). Cancer immunotherapy by immune checkpoint targeting has shown impressive clinical outcomes, but requires substantial improvement given the limited number of patients who benefit from the treatment. Targeting the mechanisms controlling immune checkpoint expression could represent a step towards this aim. Accumulating data indicate that this strategy can limit immune checkpoint expression, in some instances simultaneously inhibiting several immune checkpoints. This review discusses various mechanisms through which IRs are activated or regulated, and ways these mechanisms could be exploited to develop more effective future immunotherapies.