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

Figure 1

Characterization of CD8⁺ T cell fates in acute and antitumor immune responses. (a) In an acute immune response, CD8⁺ T cell priming induces cytotoxic regulated by the transcription factors T-bet, Runx3, Eomes, Blimp-1, and NFAT and the cytokines IL-2 and IL-12. Following antigen clearance, contract into and . are regulated by different levels of T-bet/Eomes and Blimp-1/Bcl-6. have higher levels of Eomes and Bcl-6 as compared to and are influenced by expression of Tcf-1, WNT/β-catenin, STAT3, and STAT5, which cooperate to maintain a persistent population of with high proliferative potential. IL-7 and IL-15 maintain homeostatic proliferation of CD8⁺ memory T cells. (b) Tumor antigen primed traffic to tumors as TILs. T-bet and Blimp-1 cooperate to repress iR expression and, with Eomes, promote CTL-mediated tumor rejection. NFAT and TGF-β promote tumor cell lysis through CD103 expression. Dysfunctional TIL can become , , or . High T-bet expression maintains functional whereas high Eomes expression promotes severe exhaustion. There is complex interplay between T-bet, Blimp-1, and iRs in . result from insufficient costimulation through CD28. Unbalanced NFAT signaling induces anergy-inducing genes and, along with Ikaros, Egr1/2, and NF-κB, inhibits effector molecule expression. lack CD28 expression and may be regulated by FoxP3.