Systemic exosome abundance and comprehensive proteome profile of lymphoma-derived exosomes: Insights into host-tumor...

Exosomes are among the various secreted vesicles which play a pivotal role in tumor growth and progression. In fact, tumor-derived exosomes are considered to be an excellent reservoir of oncogenic factors which govern the metastatic potential of cancer cells. Previously, we observed systemic damage within the lymphoma-bearing host and established the immunomodulatory effect of lymphoma-derived factors/ascites on macrophages. However, whether this host-tumor interaction involves exosomes or not remains unclear. In view of this, we aimed to explore the proteomics landscape of tumor-derived exosomes to unravel their possible involvement in governing lymphoma-induced pathogenicity. Interestingly, we observed significant increase in exosome abundance in blood and tissues of lymphoma-bearing hosts. Comprehensive proteome profile of exosomes revealed a distinct set of tumor-associated proteins, such as metalloproteinases (MMPs) and myeloperoxidase, which might be mediating tissue degradation within the host. Various exosomal proteins overlapped with known markers of epithelial to mesenchymal transition (EMT) and lymphoma. Functional enrichment analysis of exosomal cargoes revealed their immunomodulatory potential which could alter the activation state of macrophages. In vitro assay confirmed active uptake of these exosomes by macrophages resulting in morphological alterations, increased reactive oxygen species (ROS) production and reduction in LPS-induced nitrite release by inhibiting NOS2 expression. Conclusively, exosome abundance in blood and tissues highlight their possible involvement in mediating systemic alterations in lymphoma-bearing hosts. This study gives the first evidence of MMP-8 within the exosomes suggesting a novel pathway for its contribution to tissue damage in cancer condition. The study underscores the possible link for exosome-macrophage crosstalk to promote systemic immunomodulation in lymphoma. Our results give key insight into exosome profiling and illustrate the presence of invasive and immunomodulatory proteins which might be used as diagnostic or prognostic markers and could serve as an important target in therapeutic intervention in cancer.