Syeda, S.; Rawat, K.; Shrivastava, A. Exosome Load Increases Systemically and Mediates Pro-tumoral M2 Macrophage Polarization in Lymphoma. Preprints2023, 2023040062. https://doi.org/10.20944/preprints202304.0062.v1
APA Style
Syeda, S., Rawat, K., & Shrivastava, A. (2023). Exosome Load Increases Systemically and Mediates Pro-tumoral M2 Macrophage Polarization in Lymphoma. Preprints. https://doi.org/10.20944/preprints202304.0062.v1
Chicago/Turabian Style
Syeda, S., Kavita Rawat and Anju Shrivastava. 2023 "Exosome Load Increases Systemically and Mediates Pro-tumoral M2 Macrophage Polarization in Lymphoma" Preprints. https://doi.org/10.20944/preprints202304.0062.v1
Abstract
Macrophages are the key effector cells of innate immunity which show two polarized states: M1, classically activated and M2, alternatively activated. Tumor-associated macrophages (TAMs) which usually show M2 polarization, are immunosuppressive cells that enhance tumor metastasis and invasion. Also, enrichment of TAMs is known to be closely associated with poor prognosis of cancer patients. Therefore, TAMs are considered to be promising targets for immunotherapy. Importantly, tumor-derived exosomes emerged as a crucial player in immune regulation which can remodel the tumor microenvironment towards immunosuppressive state. Of note, few studies have shown that exosomes could induce polarization of macrophages towards M2 type in tumor condition, while others showed activation of M1 or mixed phenotype. Considering the role of TAMs in cancer, there is an urgent need to decipher the exosome-mediated cross-talk between tumor cells and macrophages.For this, we used murine model of Dalton’s lymphoma (DL), wherein, firstly, we evaluated increased exosome burden by assessing exosome level in serum as well as in various tissues of tumor-bearing host. Next, proteomic profiling of lymphoma-derived exosomes was done which revealed the presence of immunomodulatory proteins. Of note, these proteins were known to alter the macrophage polarization. In order to assess the effect of these exosomes on macrophages, we performed in vitro study using RAW264.7 cells. In vitro study revealed that frequent uptake of exosomes mediated a morphological change in macrophages which reduced their phagocytic activity. In parallel, exosomes increased reactive oxygen species (ROS) level and inhibited LPS-induced nitric oxide (NO) level in macrophages. Also, exosomes upregulated the expression of arginase-1 (an M2 marker) in macrophages but decreased the LPS-induced nitric oxide synthase 2 (NOS2) (an M1 marker) expression. Moreover, we observed a pro-tumoral cytokine profile in macrophages incubated with exosomes. Our study suggests that exosome load increases in lymphoma-bearing hosts systemically. Importantly, lymphoma-derived exosomes mediate the activation of macrophages towards pro-tumoral M2 type. Our results give an insight into the exosome-mediated tumor and immune cell cross-talk which could serve as an important prospect for targeting in cancer immunotherapy.
Biology and Life Sciences, Immunology and Microbiology
Copyright:
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