Table 2.

Immunological effects of blocking exosomal PD-L1.

Cancer type	Experimental setting	Effect	Reference
HNSCC	Exosomal PD-L1 was isolated from the plasma of HNSCC patients and coincubated with activated CD8 + T cells ± PD − 1 inhibitor.	Exosomal PD-L1 downregulates CD69 expression which is upregulated after PD-1 blockade.	[64]
GC	Exosomal PD-L1 was isolated from the CCM of MNK74 cells and coincubated with Jurkat T cells and PBMC ± Nivolumab.	Exosomal PD-L1 induces Jurkat T cell apoptosis and downregulates CD69 and CD25 expression in PBMC; both effects were reversed after PD-1 blockade.	[41]
Glioblastoma	Exosomal PD-L1 was isolated from CCM of PCC derived from glioblastoma patients and coincubated with activated CD4+ and CD8 + T cells ± PD − 1 antibodies.	PD-1 blockade restores T cell activation as measured by CD69 and CD25 expression.	[15]
Melanoma	Exosomal PD-L1 isolated from PD-L1/MEL624 cells was preincubated with anti-PD-L1 antibodies and then incubated with activated CD8+ T cells.	Exosomal PD-L1 blockade restored T cell proliferation, granzyme B, IFN-γ, IL-2, and TNF-α production.	[12]
NSCLC	Exosomal PD-L1 isolated from H460 and H1975 cells was preincubated with anti-PD-L1 antibodies and then incubated with activated Jurkat T cells.	Exosomal PD-L1 decreased the IFN-γ production in a dose-dependent manner, while PD-L1 blockade restored IFN-γ secretion.	[28]

HNSCC: head and neck squamous cell cancer; GC: gastric cancer; CCM: cell culture medium; PBMC: peripheral blood mononuclear cells; PCC: primary cell culture; IFN-γ: interferon-γ; TNF-α: tumor necrosis factor-α; IL-2: interleukin-2; NSCLC: non-small-cell lung cancer.