T-Cell-Derived Exosomes From Multi Core Granules Exhibit Superior Caspase-3-Mediated Tumor-Suppressive Activity

Nadia Alawar1, Claudia Schirra1, Ruth Rasuli1,2

  • 1Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, Homburg, Germany.

PubMed

Insights

Cytotoxic T lymphocyte (CTL)-derived exosomes originate from distinct cellular pathways. Multicore granule-derived exosomes show higher tumor cell killing potential, offering new immunotherapy strategies.

Area of Science:

  • Immunology
  • Cell Biology
  • Extracellular Vesicles

Background:

  • Small extracellular vesicles (sEVs) from cytotoxic T lymphocytes (CTLs) are implicated in antitumor immunity.
  • The precise intracellular origins and functional roles of CTL-derived exosomes are not fully understood.

Purpose of the Study:

  • To investigate the intracellular routes of CTL-derived exosome biogenesis.
  • To characterize the cytotoxic potential and release mechanisms of different CTL exosome populations.

Main Methods:

  • Correlative light and electron microscopy to identify exosome origins.
  • Total internal reflection fluorescence microscopy to observe exosome release at the immunological synapse.
  • Scalable primary cell culture and super-resolution microscopy for exosome isolation and characterization.

Main Results:

  • CTL-derived exosomes originate from multivesicular bodies (MVBs) and multicore granules (MCGs).
  • MCG-derived exosomes are released at the immunological synapse in a stimulus-dependent manner.
  • MCG-derived exosomes exhibit significantly higher cytotoxic activity against tumor cells via caspase 3-dependent apoptosis compared to MVB-derived exosomes.

Conclusions:

  • CTLs utilize distinct secretory pathways (MVBs and MCGs) to produce heterogeneous exosome populations.
  • MCG-derived exosomes possess potent cytotoxic properties, suggesting their potential as targeted cancer immunotherapies.
  • Understanding these pathways provides insights into CTL-mediated immunity and novel therapeutic development.

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