Effector, Memory, and Dysfunctional CD8⁺ T Cell Fates in the Antitumor Immune Response

Table 1

Classification of human CD8⁺ T cell fates based on surface markers, transcription profiles, and observed phenotype.

CD8^+ T cell fate	Surface marker profile	Transcription profile	Phenotype
Effector [18–22]	(i) KLRG1^+; (ii) CD43^+; (iii) CD62L^−; (iv) CD69^+; (v) CD95^+; (vi) CD137^+	(i) T-bet/Eomes; (ii) Blimp-1; (iii) Runx3; (iv) Stat4/Stat5; (v) Id2	(i) Direct cytotoxicity against transformed and virus-infected cells; (ii) Mediate cytotoxicity through Fas/FasL and granzyme/perforin
Central memory [23–28]	(i) CCR7^+; (ii) CD44^+; (iii) CD45RO^+; (iv) CD62L^+; (v) CD122^+; (vi) CD127^+; (vii) IL15R^+	(i) T-bet/Eomes; (ii) Bcl6; (iii) Tcf1; (iv) Stat3; (v) Id3; (vi) WNT-β-catenin	(i) Less differentiated; (ii) Residing in lymph nodes, spleen, bone marrow, and blood; (iii) No immediate effector function; (iv) Differentiating into upon antigen rechallenge; (v) Self-renewal capacity; (vi) IL-7/IL-15 dependence
Effector memory [23–28]	(i) CCR7^−; (ii) CD44^+; (iii) CD45RO^+; (iv) CD62L^−; (v) CD127^+; (vi) KLRG1^+	(i) T-bet/Eomes; (ii) Blimp-1/Bcl-6	(i) Found in both lymphoid and peripheral tissues; (ii) Rapidly release effector molecules; (iii) Highly cytotoxic; (iv) Intermediate differentiation stage; (v) Rapidly differentiate into upon antigen rechallenge
Exhausted [29–33]	(i) CD45RO^+; (ii) CD57^+; (iii) CD95^+; (iv) PD-1^+; (v) CTLA-4^+; (vi) Tim-3^+; (vii) Lag-3^+; (viii) BTLA^+	(i) NFAT; (ii) T-bet/Eomes; (iii) Blimp-1; (iv) BATF; (v) FoxP1	(i) Reduced proliferation; (ii) Decreased cytokine production; (iii) Reduced cytotoxicity; (iv) Reduced IFNγ and IL-2 secretion; (v) Eventual cell death
Anergic/tolerant [34–41]	(i) Lag-3^+; (ii) PD-1^+	(i) NFAT; (ii) NF-kB/RelA; (iii) Ikaros; (iv) Egr1/Egr2	(i) Reduced IL-2 secretion; (ii) Reduced proliferation
Senescent/regulatory [42–44]	(i) KLRG1^+; (ii) CD28^−; (iii) CD57^+	(i) FoxP3	(i) Cell-cycle arrest; (ii) Immunosuppressive