Science_-_7_February_2020_UserUpload.Net

Kalluriet al.,Science 367 , eaau6977 (2020) 7 February 2020 6of15

Fig. 5. Regulation of
immune response by
exosomes.Exosomes
from distinct cellular
sources, including
immune cells (B cells and
dendritic cells), cancer
cells, epithelial, and
mesenchymal cells, shed
exosomes with cargos
that can influence the
proliferation and respec-
tive activity of recipient
cells of both the innate
and adaptive immune
system. CD4+and CD8+
T cells [cytotoxic T cells
(CTL)] can be directly or
indirectly influenced by
exosomes, stimulating or
suppressing their prolifer-
ation and function(s).
PBMC, peripheral blood
mononuclear cell; X?,
other potential immuno-
modulatory proteins.

B cells

Primed dendritic cells

and other APCs

Cancer cells

Modified epithelial,

mesenchymal, and

other immune cells

Mesenchymal

stem cells

Engineered

immunomodulatory

exosomes

CD4O

ligand

Macrophage

Cancer exosomes

MHC II

CD4/CTL

CD4/CD8/CTL

CD8

APCs NK cells Cancer cells

MSC

CD8/CD86

Dendritic cells

exosomes (DEX)

PD-L1 NK cells

Macrophage

(donor

dependent)

No impact on

immune cells

(donor

dependent)

CD8/CTL CD4 T effectors

PBMC

(donor

dependent)

CD4/CD8/CTL

CD4//CTL

CD4/CTL

CD8

CD4 TReg CD8

DCs/APCs

Primed DCs APCs

MHC I/MHC II

Icam-1

DNA

Hsp70

MHC I Neoantigen

X?

PDL1

RESEARCH | REVIEW