Table 3 Reprogramming pathways or metabolism to avoid and reinvigorate CD8⁺ T cell exhaustion

Avoiding T cell exhaustion

MEKi

-

ex vivo

-

MEK

[84]

MEKi with selumetinib and anti-CTLA-4

HPMC

in vivo

subcutaneous injection, oral administration, and intraperitoneal injection

-

[91]

Anti-PD-1 and anti-Tim-3

-

in vitro

-

PD-1, PD-L1, Tim-3, and Tim-3L

[89, 92, 93, 99]

MTA and SAM

-

in vitro, ex vivo

-

CD2, CD3, and CD28

[94]

Reinvigorating T cell exhaustion

Anti-PD-1 and anti-CTLA-4

-

ex vivo

-

CD28, CD3, PD-1, and CTLA-4

[86, 89, 92, 95]

Pembrolizumab, Pidilizumab and Nivolumab

-

ex vivo, in vitro

-

PD-1 and PD-L1

[97]

NR4A and NFAT inhibitor

-

in vivo

intravenous injection

NR4A and NFAT transcription factor

[98]