c-Jun overexpression in CAR T cells induces exhaustion resistance
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Chimeric antigen receptor (CAR) T cells mediate anti-tumour effects in a small subset of patients with cancer 1-3, but dysfunction due to T cell exhaustion is an important barrier to progress 4-6. To investigate the biology of exhaustion in human T cells expressing CAR receptors, we used a model system with a tonically signaling CAR, which induces hallmark features of exhaustion 6. Exhaustion was associated with a profound defect in the production of IL-2, along with increased chromatin accessibility of AP-1 transcription factor motifs and overexpression of the bZIP and IRF transcription factors that have been implicated in mediating dysfunction in exhausted T cells 7-10. Here we show that CAR T cells engineered to overexpress the canonical AP-1 factor c-Jun have enhanced expansion potential, increased functional capacity, diminished terminal differentiation and improved anti-tumour potency in five different mouse tumour models in vivo. We conclude that a functional deficiency in c-Jun mediates dysfunction in exhausted human T cells, and that engineering CAR T cells to overexpress c-Jun renders them resistant to exhaustion, thereby addressing a major barrier to progress for this emerging class of therapeutic agents.
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T cell exhaustion limits the efficacy of chimeric antigen receptor (CAR) T cell therapy against solid tumours.
“T cell exhaustion also limits the efficacy of chimeric antigen receptor (CAR) T cell therapy against solid tumours14–17.”
From Proteotoxic stress response drives T cell exhaustion and immune evasion (2025) · cites this paper as [14]
Next-generation T cell therapies are being engineered with transgenes designed to overcome suppressive signals in the tumor environment.
“Next-generation T cell therapies are being engineered with transgenes designed to overcome suppressive signals in the tumor environment (Kloss et al., 2018; Lynn et al., 2019; Yamamoto et al., 2019).”
From Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies (2020) · cites this paper as Lynn et al., 2019
c-Jun overexpression protects CAR-T cells from dysfunction by inducing T-cell exhaustion resistance.
“c-Jun overexpression protects CAR-T cells from dysfunction by inducing T-cell exhaustion resistance [157].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [157]
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Wang, S.-W., Gao, C., Zheng, Y.-M., Yi, L., Lu, J.-C., Huang, X.-Y., Cai, J.-B., Zhang, P.-F., Cui, Y.-H., & Ke, A.-W. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01518-8 · Cited by 478 · see citing works
“Similarly, CAR-T cells also acquire a depleted phenotype when entering the TME in vivo, which has become a major obstacle to CAR-T cell therapy [197, 198].”
BackgroundImproving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion
Gumber, D., & Wang, L. D. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103941 · Cited by 409 · see citing works
An NK-like CAR T cell transition in CAR T cell dysfunction
Good, C. R., Aznar, M. A., Kuramitsu, S., Samareh, P., Agarwal, S., Donahue, G., Ishiyama, K., Wellhausen, N., Rennels, A. K., Ma, Y., et al. (2021) · Cell · doi:10.1016/j.cell.2021.11.016 · Cited by 397 · see citing works
CAR T Cell Therapy for Solid Tumors: Bright Future or Dark Reality?
Wagner, J., Wickman, E., DeRenzo, C. C., & Gottschalk, S. M. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.09.015 · Cited by 383 · see citing works
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“that manipulating this processmay lead to the improved efficacy of T cell responses in cancer (Sakuishi et al., 2010; Long et al., 2015; Fraietta et al., 2018a, 2018b; Ribas and Wolchok, 2018; Lynn et al., 2019; Yost et al., 2019; Weber et al., 2021).”
BackgroundSelf-citationEngineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing
Dimitri, A. J., Herbst, F., & Fraietta, J. A. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01559-z · Cited by 370 · see citing works
BATF and IRF4 cooperate to counter exhaustion in tumor-infiltrating CAR T cells
Seo, H., González‐Avalos, E., Zhang, W., Ramchandani, P., Yang, C., Lio, C. J., Rao, A., & Hogan, P. G. (2021) · Nature Immunology · doi:10.1038/s41590-021-00964-8 · Cited by 353 · see citing works
Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity
Prinzing, B., Zebley, C. C., Petersen, C. T., Fan, Y., Anido, A. A., Yi, Z., Nguyen, P., Houke, H., Bell, M., Haydar, D., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abh0272 · Cited by 349 · see citing works
“We and others have observed differential in vitro and in vivo requirements for exogenous cytokines of CAR T cells with second genetic modifications (47, 60), highlighting differences between in vitro culture systems and preclinical in vivo models, which more closely mimic human”
BackgroundA blood atlas of COVID-19 defines hallmarks of disease severity and specificity
Ahern, D. J., Ai, Z., Ainsworth, M., Allan, C., Allcock, A., Angus, B., Ansari, M. A., Arancibia-Cárcamo, C. V., Aschenbrenner, D., Attar, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.012 · Cited by 328 · see citing works
“AP-1 is a pioneer transcription factor that reversibly imprints the senescence enhancer landscape following stress and can be modulated to reverse T cell exhaustion (Lynn et al., 2019; Martı́nez-Zamudio et al., 2020).”
BackgroundCo-opting signalling molecules enables logic-gated control of CAR T cells
Tousley, A. M., Rotiroti, M. C., Labanieh, L., Rysavy, L. W., Kim, W., Lareau, C. A., Sotillo, E., Weber, E. W., Rietberg, S. P., Dalton, G. N., et al. (2023) · Nature · doi:10.1038/s41586-023-05778-2 · Cited by 336 · see citing works
Self-citationEpigenetic regulation of T cell exhaustion
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CRISPR activation and interference screens decode stimulation responses in primary human T cells
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“Recent preclinical work (42) highlights c-JUN overexpression to limit T cell exhaustion and further enhance cell therapies.”
BackgroundEarly precursor T cells establish and propagate T cell exhaustion in chronic infection
Utzschneider, D. T., Gabriel, S. S., Chisanga, D., Gloury, R., Gubser, P. M., Vasanthakumar, A., Shi, W., & Kallies, A. (2020) · Nature Immunology · doi:10.1038/s41590-020-0760-z · Cited by 306 · see citing works
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
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A second-generation M1-polarized CAR macrophage with antitumor efficacy
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“Recently, it has been reported that CAR T cells engineered to express supporting cytokines 29–31 , checkpoint blockade antibody 32 or c-Jun 33 or targeting a CAR to the TRAC locus 34 resist exhaustion or dysfunction.”
CAR-T cell therapy for cancer: current challenges and future directions
Zugasti, I., Espinosa-Aroca, L., Fidyt, K., Mulens‐Arias, V., Díaz‐Beyá, M., Juan, M., Urbano-Ispizúa, Á., Esteve, J., Velasco-Hernández, T., & Menéndez, P. R. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02269-w · Cited by 332 · see citing works
Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers
Steffin, D., Ghatwai, N., Montalbano, A., Rathi, P., Courtney, A. N., Arnett, A., Fleurence, J., Sweidan, R., Wang, T., Zhang, H., et al. (2024) · Nature · doi:10.1038/s41586-024-08261-8 · Cited by 300 · see citing works
“CAR T cells co-expressing JUN had increased antitumour activity in non-clinical models 41 , and our results demonstrate the importance of FOS and JUN subfamily members, because these genes were significantly upregulated in tumour-infiltrating 15.CAR T cells in responders.”
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Promises and challenges of adoptive T-cell therapies for solid tumours
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Anti-GD2 synergizes with CD47 blockade to mediate tumor eradication
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Self-citationEpigenetic scars of CD8+ T cell exhaustion persist after cure of chronic infection in humans
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FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy
Chan, J. D., Scheffler, C. M., Munoz, I., Sek, K., Lee, J. N., Huang, Y., Yap, K. M., Saw, N. Y. L., Li, J., Chen, A. X. Y., et al. (2024) · Nature · doi:10.1038/s41586-024-07242-1 · Cited by 251 · see citing works
“We compared FOXO1-ADA-overexpressing CAR T cells with CAR T cells overexpressing TCF7, ID3 and JUN, given previous data indicating the enhanced efficacy of JUN-overexpressing CAR T cells 22 .”
Post-infusion CAR TReg cells identify patients resistant to CD19-CAR therapy
Good, Z., Spiegel, J. Y., Sahaf, B., Malipatlolla, M. B., Ehlinger, Z. J., Kurra, S., Desai, M. H., Reynolds, W. D., Lin, A. W., Vandris, P., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01960-7 · Cited by 250 · see citing works
Self-citationCellular networks controlling T cell persistence in adoptive cell therapy
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RASA2 ablation in T cells boosts antigen sensitivity and long-term function
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Self-citationImpact of the Human Cell Atlas on medicine
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‘Stem-like’ precursors are the fount to sustain persistent CD8+ T cell responses
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FOXO1 is a master regulator of memory programming in CAR T cells
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Self-citationEnhanced safety and efficacy of protease-regulated CAR-T cell receptors
Labanieh, L., Majzner, R. G., Klysz, D. D., Sotillo, E., Fisher, C., Vilches-Moure, J. G., Pacheco, K. Z., Malipatlolla, M. B., Xu, P., Hui, J. H., et al. (2022) · Cell · doi:10.1016/j.cell.2022.03.041 · Cited by 227 · see citing works
“…et al., 2019) GSE136891 Experimental models: Cell lines Nalm6-GL (Majzner et al., 2019) N/A Nalm6-B7H3 (Majzner et al., 2019) N/A 143B-GL (Lynn et al., 2019) N/A MED8A-GL This paper N/A Nalm6- B7H3 High (Majzner et al., 2019) N/A CHLA255-GL (Majzner et al., 2020) N/A (Continued on next…”
BackgroundMethodInfluentialSelf-citationStem-like exhausted and memory CD8+ T cells in cancer
Gebhardt, T., Park, S. L., & Parish, I. A. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00615-0 · Cited by 216 · see citing works
“…CAR constructs to the endogenous TCR locus 254 , to limit terminal exhaustion; and the rational knockout or over-expression of transcription factors 255–257 , epigenetic regulators 108,258,259 , engineered cytokine receptors 260,261 and other factors 227,262,263 to enrich stem-like populations.”
BackgroundImmunotherapy of multiple myeloma
Minnie, S. A., & Hill, G. R. (2020) · Journal of Clinical Investigation · doi:10.1172/jci129205 · Cited by 216 · see citing works
“Additional approaches to improve CAR T cell quality include selecting for naive or stem/memory T cells (158), engineering of CAR T cells for exhaustion resistance (170), administration of defined compositions of CD4+/CD8+ T cells (164), and informed selection of costimulatory domains for CD28 (brisk T cell proliferati…”
BackgroundIn vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer
Chen, Z., Arai, E., Khan, O., Zhang, Z., Ngiow, S. F., He, Y. M., Huang, H., Manne, S., Cao, Z., Baxter, A. E., et al. (2021) · Cell · doi:10.1016/j.cell.2021.02.019 · Cited by 201 · see citing works
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“More recently, it was shown that overexpression of canonical AP-1 factor c-Jun in CAR-T cells induced exhaustion resistance (Lynn et al., 2019).”
BackgroundStraathof, K. C. M., Flutter, B. R., Wallace, R., Jain, N., Loka, T., Depani, S., Wright, G., Thomas, S., Cheung, G. W.-K., Gileadi, T. E., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abd6169 · Cited by 202 · see citing works
“have been challenged (33) and have not been replicated (34).”
BackgroundImmune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases
Song, P., An, J., & Zou, M.-H. (2020) · Cells · doi:10.3390/cells9030671 · Cited by 198 · see citing works
“Importantly, c-Jun overexpression protects CAR-T cells from dysfunction by inducing T-cell exhaustion resistance [157].”
BackgroundAntigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells
Singh, N., Frey, N. V., Engels, B., Barrett, D. M., Shestova, O. E., Ravikumar, P., Cummins, K. D., Lee, Y. G., Pajarillo, R., Chun, I., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01326-5 · Cited by 197 · see citing works
Arming CAR-T cells with cytokines and more: Innovations in the fourth-generation CAR-T development
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Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness
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“4,5 Alternatively, inef fi cient CAR tonic signaling can also lead to limited ef fi cacy.”
Engineered skin bacteria induce antitumor T cell responses against melanoma
Chen, Y. E., Bousbaine, D., Veinbachs, A., Atabakhsh, K., Dimas, A., Yu, V. K., Zhao, A., Enright, N. J., Nagashima, K., Belkaid, Y., et al. (2023) · Science · doi:10.1126/science.abp9563 · Cited by 191 · see citing works
Androgen receptor-mediated CD8+ T cell stemness programs drive sex differences in antitumor immunity
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Targeting public neoantigens for cancer immunotherapy
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Pooled Knockin Targeting for Genome Engineering of Cellular Immunotherapies
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A genome-scale screen for synthetic drivers of T cell proliferation
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Next-Generation CAR T-cell Therapies
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Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies
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“To better understand the mechanisms leading to exhaustion, Lynn et al. 59 recently developed a cellular model of exhaustion by introducing a tonic signalling CAR (HA-28z CAR) into T cells.”
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Inosine induces stemness features in CAR-T cells and enhances potency
Klysz, D. D., Fowler, C., Malipatlolla, M. B., Stuani, L., Freitas, K. A., Chen, Y., Meier, S. L., Dániel, B., Sandor, K. D., Xu, P., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.01.002 · Cited by 178 · see citing works
Self-citationCounteracting CAR T cell dysfunction
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“These cells showed different chromatin accessibility, enhanced expansion and functional capacity, and improved anti-tumor activity in five different tumor mouse models in vivo (189).”
BackgroundCD8+ T cell exhaustion and cancer immunotherapy
Wang, Q., Qin, Y., & Li, B. (2023) · Cancer Letters · doi:10.1016/j.canlet.2022.216043 · Cited by 155 · see citing works
Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells
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Enhanced T cell effector activity by targeting the Mediator kinase module
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“Stimulation of CD19-28z CAR T cells via the CAR resulted in higher levels of pS6 inMED12deficient cells, demonstrating enhanced antigendependent activation of the mammalian target of rapamycin complex 1(MTORC1) pathway which may contribute to the increased metabolic activity observed (fig.”
BackgroundMethodInfluentialSelf-citationGreco, B., Malacarne, V., Girardi, F. D., Scotti, G. M., Manfredi, F., Angelino, E., Sirini, C., Camisa, B., Falcone, L., Moresco, M. A., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abg3072 · Cited by 154 · see citing works
“In line with this notion, CAR T cell therapy can greatly benefit from disruption of inhibitory pathways, either through checkpoint blockades or by pursuing genetic strategies for counteracting their signaling (60, 61).”
BackgroundTET2 guards against unchecked BATF3-induced CAR T cell expansion
Jain, N., Zhao, Z., Feucht, J., Koche, R. P., Iyer, A., Dobrin, A., Mansilla‐Soto, J., Yang, J. L., Zhan, Y. A., Lopez, M. A., et al. (2023) · Nature · doi:10.1038/s41586-022-05692-z · Cited by 154 · see citing works
The potential of activator protein 1 (AP-1) in cancer targeted therapy
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“c-Jun overexpression can exhibit CAR-T cell exhaustion resistance, improve expansion potential, reduce terminal differentiation, and improve its anti-tumor potency in in vivo models (103).”
BackgroundInfluentialNeuropilin-1 is a T cell memory checkpoint limiting long-term antitumor immunity
Liu, C., Somasundaram, A., Manne, S., Gocher, A. M., Szymczak-Workman, A. L., Vignali, K. M., Scott, E. N., Normolle, D. P., John Wherry, E., Lipson, E. J., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0733-2 · Cited by 151 · see citing works
Exhaustion of CAR T cells: potential causes and solutions
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“It should be noted that CAR T cells engineered to overexpress c-Jun for recovery of canonical AP-1 function were shown to have enhanced expansion potential, increased functional capacity, diminished exhausted phenotype, and improved anti-tumor potency in vivo [34].”
BackgroundInfluentialPTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity
Wiede, F., Lu, K., Du, X., Zeissig, M. N., Xu, R., Goh, P. K., Xirouchaki, C. E., Hogarth, S. J., Greatorex, S., Sek, K., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0694 · Cited by 140 · see citing works
BATF3 programs CD8+ T cell memory
Ataide, M. A., Komander, K., Knöpper, K., Peters, A. E., Wu, H., Eickhoff, S., Gogishvili, T., Weber, J., Grafen, A., Kallies, A., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0786-2 · Cited by 137 · see citing works
In vivo CAR engineering for immunotherapy
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“By contrast, exhaustion has been observed in ex vivo-generated autologous CAR-T cells before infusion, owing to their prolonged activation and expansion ex vivo, thereby reducing their effectiveness upon reinfusion 112,113 .”
Co-Stimulatory Receptor Signaling in CAR-T Cells
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“Overexpression of c-Jun prevented exhaustion by displacing the immunoregulatory complexes from chromatin in a tonically signaling CD28ζ CAR-T cell model [180].”
BackgroundEngineered CD47 protects T cells for enhanced antitumour immunity
Yamada‐Hunter, S. A., Theruvath, J. L., McIntosh, B. J., Freitas, K. A., Lin, F. H. S., Radosevich, M., Leruste, A., Dhingra, S., Martínez-Vélez, N., Xu, P., et al. (2024) · Nature · doi:10.1038/s41586-024-07443-8 · Cited by 142 · see citing works
Self-citationNon-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia
Leick, M. B., Silva, H. J., Scarfò, I., Larson, R. C., Choi, B. D., Bouffard, A. A., Gallagher, K., Schmidts, A., Bailey, S. R., Kann, M. C., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.04.001 · Cited by 138 · see citing works
T cell dysfunction and therapeutic intervention in cancer
Zebley, C. C., Zehn, D., Gottschalk, S. M., & Chi, H. (2024) · Nature Immunology · doi:10.1038/s41590-024-01896-9 · Cited by 142 · see citing works
Targeting the tumor microenvironment in B-cell lymphoma: challenges and opportunities
Liu, Y., Zhou, X., & Wang, X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01134-x · Cited by 139 · see citing works
“It was confirmed that engineered CAR-T cells to overexpress c-Jun could decrease or displace AP-1i from chromatin, thereby preventing T cell exhaustion [130].”
BackgroundThe current state and future of T-cell exhaustion research
Jenkins, E. M., Whitehead, T., Fellermeyer, M., Davis, S. J., & Sharma, S. (2023) · Oxford Open Immunology · doi:10.1093/oxfimm/iqad006 · Cited by 136 · see citing works
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“In particular, a recently proposed innovative strategy relies on CAR T cells over-expressing C-Jun, a transcription factor belonging to the AP-1 family, that resulted in resistance to exhaustion, enhanced in vivo expansion, reduced terminal differentiation and higher anti-tumor potency (52).”
MethodYoshikawa, T., Wu, Z., Inoue, S., Kasuya, H., Matsushita, H., Takahashi, Y., Kuroda, H., Hosoda, W., Suzuki, S., & Kagoya, Y. (2021) · Blood · doi:10.1182/blood.2021012714 · Cited by 131 · see citing works
Direct in vivo CAR T cell engineering
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“have shown that CAR T cells engineered to overexpress c-Jun are resistant to exhaustion, suggesting that the JNK/c-Jun pathway is a suitable target for immunotherapy-based combination approaches to reinvigorate anti-tumor immune functions [30].”
BackgroundInfluentialAdvancing CAR T cell therapy through the use of multidimensional omics data
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“We next examined the patterns of AP-1 protein expression and their interactions, specifically with c-Jun, due to their importance in the regulation of T-cell phenotype and function 43 .”
BackgroundImmune receptor inhibition through enforced phosphatase recruitment
Fernandes, R. A., Su, L., Nishiga, Y., Ren, J., Bhuiyan, M. A., Cheng, N., Kuo, C. J., Picton, L. K., Ohtsuki, S., Majzner, R. G., et al. (2020) · Nature · doi:10.1038/s41586-020-2851-2 · Cited by 124 · see citing works
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Immune determinants of CAR-T cell expansion in solid tumor patients receiving GD2 CAR-T cell therapy
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“…ATAC-seq also demonstrated limited differences in the open chromatin (Figures 2F and S4), but showed enrichment in good expander CAR-T products of AP-1 factor transcription factor (TF) motifs, such as BATF, JUN, and FOS, signals previously implicated in exhaustion-resistant T cells 29 (Figure 2G).”
BackgroundSelf-citation
- Authors
- Lynn, R. C., Weber, E. W., Sotillo, E., Gennert, D., Xu, P., Good, Z., Anbunathan, H., Lattin, J., Jones, R., Tieu, V., Nagaraja, S., Granja, J., de Bourcy, C. F. A., Majzner, R., Satpathy, A. T., Quake, S. R., Monje, M., Chang, H. Y., & Mackall, C. L.
- Affiliations
- Lyell Immunopharma (United States) (US)
- Stanford Medicine (US)
- Stanford University (US)
- Parker Institute for Cancer Immunotherapy (US)
- Chan Zuckerberg Biohub San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Mackall, Crystal L.
- ORCID
- Venue
- Nature
- Published
- 2019-12-04
- Volume
- 576
- Issue
- 7786
- Pages
- 293-300
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6944329
- OpenAlex
- W2992738455
- Cited by
- 891
- References
- 63
- Citations by year
- 2026: 141 · 2025: 151 · 2024: 138 · 2023: 129 · 2022: 122 · 2021: 119 · 2020: 89 · 2019: 1 · 2012: 1
- FWCI
- 34.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1s10od018220-01)
- National Human Genome Research Institute (RM1HG007735, P50HG007735)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- c-Jun, chimeric antigen receptor T cells, T cell exhaustion, AP-1 transcription factor, IL-2 deficiency, chromatin accessibility, IRF transcription factors, bZIP transcription factors, T cell expansion, antitumor immunity, CAR-T cell engineering
- MeSH terms
- Animals, Gene Expression Regulation, Humans, Neoplasms, Receptors, Antigen, T-Cell, Transcription, Genetic, Proto-Oncogene Proteins c-jun, Transcription Factor AP-1, Epigenesis, Genetic, Cell Line, Tumor, Mice
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