Table 1.
Summary of cancer-derived exosome mediated immune interactions with oncological therapies.
| Treatment | Therapeutic interactions | Cell lines | Study design | References |
|---|---|---|---|---|
| ICI immunotherapy | CDEX-PD-L1 reduces ICI efficacy | • Human prostate cancer and melanoma • Murine prostate cancer |
in vitro, in vivo and ex vivo | (85) |
| • Pre-treatment CDEX-PD-L1 predicts response to ICI | • Human melanoma | in vivo | (86) | |
| • CDEX-PD-L1 changes during treatment correlate to efficacy | • Human melanoma • Human HNSCC |
in vivo in vivo |
(86) (89) |
|
| CDEX-PD-L1 is prognostic irrespective of ICI treatment | • Human HNSCC | in vivo | (90) | |
| Cellular immunotherapy | CDEX induces reduced adoptive NK cell cytotoxicity (including reduced NKG2D) | • Human acute myeloid leukemia | in vitro | (92) |
| Radiation | Expansion of CDEX population | (multiple) | (93–98) | |
| • p53 regulated response | • Human and murine GBM • Human prostate cancer |
in vitro | (93, 94) | |
| Modulation of CDEX cargo | ||||
| • Protein upregulation | • Human HNSCC | in vitro | (99) | |
| • miRNA upregulation | • Human neuroblastoma, GBM and malignant nerve sheath tumor | in vitro | (100) | |
| • Dose dependent changes | • Murine non-malignant splenocytes and bone marrow cells | in vivo | (104) | |
| CDEX-mediated upregulation of regulatory pathways (TGF-β, STAT and Notch) | • Human neuroblastoma, GBM and malignant nerve sheath tumor | in vitro | (100) | |
| Upregulation of DAMP pathways (HSP, HMGB1, calreticulin) | • Human prostate cancer • Human GBM • Murine melanoma |
in vitro and in vivo | (101, 108, 109) | |
| • Naïve DC activation | • Murine melanoma | in vitro | (109) | |
| • MDSC activation | • Murine renal cancer | in vivo | (112) | |
| Cytotoxic chemotherapy | Expansion of CDEX population | (multiple) | (128–132) | |
| Modulation of CDEX cargo | ||||
| • Heparinase (extracellular matrix degradation) | • Human myeloma | in vitro | (128) | |
| • Annexin A6 (pro-metastasis) | • Human breast cancer and melanoma • Murine breast cancer |
in vitro and in vivo | (129) | |
| CDEX-HSP70 and MDSC activation | • Murine melanoma and lymphoma | in vitro and in vivo | (134) | |
| CDEX-DNA mediated STING-dependent DC stimulation | • Murine breast cancer | in vitro | (133) | |
CDEX, cancer-derived exosome; DAMP, damage associated molecular pattern; DC, dendritic cell; GBM, glioblastoma multiforme; HMGB1, high mobility group box 1 protein; HNSCC, head and neck squamous cell carcinoma; HSP, heat shock protein; ICI, immune checkpoint inhibitors; MDSC, myeloid derived suppressor cell; PD-L1, programmed death ligand 1; STAT, signal transducer and activator of transcription; STING, stimulator of interferon genes.