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. 2021 Nov;41(11):1228-1231.
doi: 10.1002/cac2.12222. Epub 2021 Sep 23.

Transcriptional suppression of CD8+ T cell exhaustion for improving T cell immunotherapy

Xue Yang  1 , Bingjing Wang  1 , Xuetao Cao  1   2
Affiliations

Transcriptional suppression of CD8+ T cell exhaustion for improving T cell immunotherapy

Xue Yang et al. Cancer Commun (Lond). 2021 Nov.
No abstract available

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Figures

FIGURE 1
FIGURE 1
The transcription factor BATF epigenetically regulating the exhaustion and differentiation of CD8+ T cells in a solid tumor model case and chronic infection case. (A) In a CAR‐T therapy of solid tumor model, BATF binds with IRF4 at AICE site to reshape the chromatin landscape, therefore, inducing chromatin accessibility changes to promote the mRNA expression of effector genes and suppress the mRNA expression of exhaustion genes. Consequently, BATF‐transduced CAR‐T cells can show enhanced anti‐tumor effect with increased TME infiltration, proliferation capacity and cytokine production, as well as the decreased exhaustion tendency. (B) In a chronic viral infection model, transcription factor BATF promotes Ly108+ progenitor T (TPRO) cell subset to differentiate into CX3CR1+ cytolytic (TEFF) cells by improving chromatin accessibility in the enhancer regions and blocks the formation of CX3CR1−Ly108− exhausted (TEXH) cells in the meantime. Abbreviations: BATF, basic leucine zipper ATF‐like transcriptional factor; AICE, AP‐1‐IRF composite element; Bhlhe40, basic helix‐loop‐helix family member e40; CAR, Chimeric antigen receptor; Ccl5, C‐C motif chemokine ligand 5; Elk4, ETS‐like transcription factor 4; Eomes, Eomesodermin; Foxo1, Forkhead box o1; E2f4, E2f transcription factor 4; Gzmb, Granzyme B; Icos, Inducible T cell costimulatory; Ifnar1, Interferon alpha and beta receptor subunit 1; IRF4, Interferon regulatory factor 4; Klf2/3, Kruppel‐like factor 2/3; Lag3, Lymphocyte activation gene 3 protein; Pd‐1, Programmed cell death‐1; Nr4a2, Nuclear receptor subfamily 4 group A member 2; Runx1, RUNX family transcription factor 1; Runx3, RUNX family transcription factor 3; Tcf‐1, T‐cell factor 1; Tim3, T cell immunoglobulin and mucin domain 3; TIL, Tumor‐infiltrating lymphocyte; Tox, Thymocyte selection‐associated high mobility group box factor.
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References

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    1. Chen Y, Zander RA, Wu X, Schauder DM, Kasmani MY, Shen J, et al. BATF regulates progenitor to cytolytic effector CD8(+) T cell transition during chronic viral infection, Nat Immunol. 2021;22:996–1007. - PMC - PubMed
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