Table 1.

Genes involved in the regulation of exhaustion and senescence pathways in T cells.

Gene name	Pathway	Mechanism of action	Study in CAR T
PD-1	Exhaustion	Immune checkpoint	Yes [9, 28–31, 35, 114–116]
CTLA-4	Exhaustion	Immune checkpoint	Yes [33, 34]
TIM-3	Exhaustion/senescence	Immune checkpoint	Yes [37]
LAG-3	Exhaustion/senescence	Immune checkpoint	No
CD160	Exhaustion	Immune checkpoint	No
VISTA	Exhaustion	Immune checkpoint	No
BTLA	Exhaustion	Immune checkpoint	No
KLRG-1	Senescence	Immune checkpoint	No
CD57	Senescence	Immune checkpoint	No
TIGIT	Exhaustion/senescence	Immune checkpoint	Yes [45]
2B4	Exhaustion	Immune checkpoint	No
CD39	Exhaustion	Immune checkpoint	No
CD73	Exhaustion	Immune checkpoint	No
c-JUN	Exhaustion	Gene expression regulation	Yes [11]
c-FOS	Exhaustion	Gene expression regulation	Yes [11]
JunB	Exhaustion	Gene expression regulation	Yes [11]
IRF4	Exhaustion	Gene expression regulation	No
BATF	Exhaustion	Gene expression regulation	Yes [11]
BATF3	Exhaustion	Gene expression regulation	Yes [11]
NFAT	Exhaustion	Gene expression regulation	No
Eomes	Exhaustion	Gene expression regulation	Yes [51]
T-bet	Exhaustion	Gene expression regulation	Yes [50]
TOX	Exhaustion	Gene expression regulation	Yes [55]
NR4A	Exhaustion	Gene expression regulation	Yes [10]
BLIMP1	Exhaustion	Gene expression regulation	No
TCF1	Exhaustion	Gene expression regulation	Yes [104]
DNMT3A	Exhaustion	Gene expression regulation	No
PI3K	Exhaustion/senescence	Signaling mediator	Yes [58, 61]
AKT	Exhaustion/senescence	Signaling mediator	Yes [57]
mTOR	Exhaustion/senescence	Signaling mediator, cell cycle regulation	Yes [5]
FOXO	Exhaustion/senescence	Signaling mediator, cell cycle regulation	Yes [50]
PTPN2	Exhaustion	Signaling mediator	Yes [68]
PP2A	Exhaustion	Signaling mediator	Yes [69]
LCK	Exhaustion	Signaling mediator	Yes [70]
SHP1/SHP2	Exhaustion	Signaling mediator	Yes [70]
A2AR	Exhaustion	Signaling mediator	Yes [76, 78]
PKA	Exhaustion	Signaling mediator	Yes [79]
TGFBR1/TGFBR2	Exhaustion	Signaling mediator	Yes [82–84]
PDK1	Exhaustion	Signaling mediator	No
PKC	Exhaustion	Signaling mediator	No
p38	Senescence	Signaling mediator	No
PIR-B	Exhaustion	Signaling mediator	No
p21CIP1	Senescence	Cell cycle regulation	No
p16INK4A	Senescence	Cell cycle regulation	No
p53	Senescence	Cell cycle regulation	No
RB	Senescence	Cell cycle regulation	No
hTERT	Senescence	Telomeres stabilization	Yes [87]
CAT	Exhaustion/senescence	Oxidative stress response	Yes [90]