Table 1.
Definitions of predysfunctional CD8+ T cell populations in chronic infection and cancer.
| Population name | Markers | Source | References |
|---|---|---|---|
| Memory-like | TCF-1+ | LCMV-c13 | (9, 39, 41, 45) |
| Human HCV | (9) | ||
| Human melanoma | (46) | ||
| Stem-like | CXCR5+TIM3− | LCMV-c13 | (44, 47) |
| Human NSCLC | (48) | ||
| PD-1+CD101−TIM3− | LCMV-c13 | (49) | |
| TIM3−CD28+ | Human kidney cancer | (50) | |
| TCF-1+ | B16-gp33 | (10) | |
| Progenitor-like | TCF-1highTIM3low | LCMV-c13 | (42) |
| Human melanoma | (42) | ||
| Tcf7+Tox+ | LCMV-c13 | (51) | |
| Progenitor | TCF-1+ | LCMV-c13 | (52–55) |
| Ly108+ (Slamf6+) | LCMV-c13 | (29) | |
| Progenitor exhausted | Slamf6+TIM3− | LCMV-c13; B16-OVA | (7) |
| TCF-1+PD-1+ | Human melanoma | (7) | |
| Precursor | T-bethighEomeslow | LCMV-c13 | (40) |
| Memory precursor-like | PD-1−TCF-1+ | MC38-OVA | (56) |
| Precursor exhausted | KLRG1-PD-1+ Ly108+ | LCMV-c13 | (57) |
| TCF-1+ | LCMV-c13 | (58) | |
| Stem cell-like exhausted | CXCR5+TIM3− | LCMV-c13 | (59) |
| Pre-exhausted | GZMK+, ZNF683+ | Human NSCLC | (60) |
| Predysfunctional | multiple | Human cancers | (61) |
| Early dysfunctional | CD38lowCD101low | ASTxCre-ERT2 | (62, 63) |
| Transitional | GZMK+ | Human melanoma | (64) |
| Human HCC | (65) | ||
| Follicular cytotoxic | CXCR5+ | LCMV-13 | (43, 66) |
| LCMV-DOCILE; HIV | (67) | ||
| Human CHB | (68) |
The listed populations have in common that they sustain the CTL response in presence of persistent antigen, and form the progenitors of the terminally exhausted population, as originally shown by Utzschneider et al. (9), Wu et al. (42), He et al. (43), and Im et al. (44) and corroborated by Miller et al. (7) and Zander et al. (29). Other cited papers consider the defined population to be predysfunctional based on the markers and the proliferative/”stem-like” phenotype described in the original papers. In the papers describing human single cell RNAseq data, the predysfunctional population is defined by intermediate expression of inhibitory receptor genes, low expression of effector-associated genes, and TCR sharing with the terminally exhausted population.