Table.1:

Role of exosomal non-coding RNAs in immune suppression in cancer

Exosomal miRNAs	Secreted cells	Recipient cells	Role and mechanism in immune suppression
miR-10a and miR-21 [229]	Glioma	MDSCs	Promote expansion and function of MDSCs. miR-10a inhibits RAR Related Orphan Receptor A (Rora), which results in the activation of NF-κB signaling. miR-21 suppresses phosphatase and tensin homolog (PTEN) expression and activates PI3K/Akt pathway in MDSCs.
miR-9 and miR-181a [230]	Breast cancer	MDSCs	miR-9 and miR-181a target suppressor of cytokine signaling-3 (SOCS3) and protein inhibitors of activated STAT 3 (PIAS3), respectively. SOCS3 and PIAS3 inhibition activates downstream JAK/STAT signaling associated with MDSC development and their suppressive effects on T cells.
miR-1246 [231]	Colon cancer	macrophages	M2 macrophages after receiving miR-1246 from p53 mutant colon cancer cells promote the development of large tumors and metastasis. miR-1246 expressing TAMs have enhanced TGFβ signaling which increases Treg population in mouse tumors and promote immune suppression.
miR-23a-3p [232]	Hepatocellular Carcinoma (HCC)	macrophages	Endoplasmic stress in HCC cells increases miR-23a-3p in HCC-derived exosomes. miR-23a-3p inhibits PTEN in recipient macrophages and induces PDL1 expression via the Akt pathway. PDL1 expressing macrophages decrease CD8+ T-cell ratio and promote T-cell apoptosis.
miR-208b [233]	Colorectal cancer (CRC)	T cells	miR-208b directly binds and inhibits programmed cell death factor 4 (PDCD4) in CD4+ T regs, which promotes their expansion. An increase in the percentage of Tregs promotes CRC growth and oxaliplatin resistance.
miR-21 [234]	EC	monocytes	EC cells transfer miR-21 to monocytes under hypoxic conditions, which transforms monocytes into M2 macrophages.
miR-107 [235]	GC	MDSC	miR-107 targets 3’UTRs of DICER and tumor suppressor gene PTEN in recipient HLA-DR−CD33+MDSCs. DICER downregulation promotes MDSCs expansion, whereas PTEN inhibition upregulates the PI3Kinase pathway and promotes proliferation.
Exosomal lncRNAs
TUC339 [236]	HCC	THP1 monocytes	TUC339 overexpression decreases production of proinflammatory cytokines IL-1β and TNF-α, T cell activator CD86 expression and phagocytic activity in THP1 cells.
RPPH1 [237]	Colorectal cancer (CRC)	macrophages	RPPH1 increases the expression of M2 macrophage markers CCL17, CCL18, CXCL8, IL-10, and TGF-β. M2 polarized macrophages promote CRC proliferation and metastasis.
SNHG16 [238]	Breast cancer	Vδ+T cells	SNHG16 sponges miR-15–5p, which blocks its inhibitory interaction with SMAD5 mRNA. SMAD5 activation induces CD73 expression. Tregs found in BC are enriched with CD73+γδ1 T cells and exert immunosuppressive functions via the adenosine pathway.
CRNDE-h [239]	CRC	CD4+ T cells	CRNDE-h binds RAR-related orphan receptor gamma (RORγT) and inhibits its binding with E3 ubiquitin ligase Itch. This prevents Itch mediated RORγT ubiquitination and degradation, which increases RORγT expression. RORγT bind to IL-17 promotor and triggers CD4 + T cell differentiation into immunosuppressive IL-17 producing Th17 cells.