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The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity

Abstract

Stem cells are maintained by transcriptional programs that promote self-renewal and repress differentiation. Here, we found that the transcription factor c-Myb was essential for generating and maintaining stem cells in the CD8+ T cell memory compartment. Following viral infection, CD8+ T cells lacking Myb underwent terminal differentiation and generated fewer stem cell–like central memory cells than did Myb-sufficient T cells. c-Myb acted both as a transcriptional activator of Tcf7 (which encodes the transcription factor Tcf1) to enhance memory development and as a repressor of Zeb2 (which encodes the transcription factor Zeb2) to hinder effector differentiation. Domain-mutagenesis experiments revealed that the transactivation domain of c-Myb was necessary for restraining differentiation, whereas its negative regulatory domain was critical for cell survival. Myb overexpression enhanced CD8+ T cell memory formation, polyfunctionality and recall responses that promoted curative antitumor immunity after adoptive transfer. These findings identify c-Myb as a pivotal regulator of CD8+ T cell stemness and highlight its therapeutic potential.

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Fig. 1: c-Myb promotes the formation of stem cell–like TCM cells by restraining terminal differentiation.
Fig. 2: c-Myb is indispensable for CD8+ T cell stemness.
Fig. 3: c-Myb enhances CD8+ T cell stemness by regulating Tcf7, Bcl2 and Zeb2 expression.
Fig. 4: Distinct functions of c-Myb domains in the regulation of CD8+ T cell differentiation and survival.
Fig. 5: Myb overexpression enhances CD8+ T cell memory and polyfunctionality.
Fig. 6: Myb overexpression enhances CD8+ T recall responses.
Fig. 7: Enforced expression of Myb enhances CD8+ T cell antitumor immunity.

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Data availability

RNA-seq data are deposited to the Gene Expression Omnibus (GEO) under accession number GSE112049. All other data that support the findings of this study are available from the corresponding author upon request.

References

  1. Simons, B. D. & Clevers, H. Strategies for homeostatic stem cell self-renewal in adult tissues. Cell 145, 851–862 (2011).

    Article  CAS  Google Scholar 

  2. Graef, P. et al. Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8+ central memory T cells. Immunity 41, 116–126 (2014).

    Article  CAS  Google Scholar 

  3. Gattinoni, L. Memory T cells officially join the stem cell club. Immunity 41, 7–9 (2014).

    Article  CAS  Google Scholar 

  4. Gattinoni, L., Speiser, D. E., Lichterfeld, M. & Bonini, C. T memory stem cells in health and disease. Nat. Med. 23, 18–27 (2017).

    Article  CAS  Google Scholar 

  5. Gattinoni, L., Klebanoff, C. A. & Restifo, N. P. Paths to stemness: building the ultimate antitumour T cell. Nat. Rev. Cancer 12, 671–684 (2012).

    Article  CAS  Google Scholar 

  6. Thaventhiran, J. E., Fearon, D. T. & Gattinoni, L. Transcriptional regulation of effector and memory CD8+ T cell fates. Curr. Opin. Immunol. 25, 321–328 (2013).

    Article  CAS  Google Scholar 

  7. Zhang, X. et al. FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Nat. Cell Biol. 13, 1092–1099 (2011).

    Article  CAS  Google Scholar 

  8. Yi, F. et al. Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal. Nat. Cell Biol. 13, 762–770 (2011).

    Article  CAS  Google Scholar 

  9. Niwa, H., Burdon, T., Chambers, I. & Smith, A. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev. 12, 2048–2060 (1998).

    Article  CAS  Google Scholar 

  10. Ying, Q. L., Nichols, J., Chambers, I. & Smith, A. BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115, 281–292 (2003).

    Article  CAS  Google Scholar 

  11. Hess Michelini, R., Doedens, A. L., Goldrath, A. W. & Hedrick, S. M. Differentiation of CD8 memory T cells depends on Foxo1. J. Exp. Med. 210, 1189–1200 (2013).

    Article  Google Scholar 

  12. Kim, M. V., Ouyang, W., Liao, W., Zhang, M. Q. & Li, M. O. The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection. Immunity 39, 286–297 (2013).

    Article  CAS  Google Scholar 

  13. Jeannet, G. et al. Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory. Proc. Natl Acad. Sci. USA 107, 9777–9782 (2010).

    Article  CAS  Google Scholar 

  14. Zhou, X. et al. Differentiation and persistence of memory CD8+ T cells depend on T cell factor 1. Immunity 33, 229–240 (2010).

    Article  CAS  Google Scholar 

  15. Cui, W., Liu, Y., Weinstein, J. S., Craft, J. & Kaech, S. M. An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity 35, 792–805 (2011).

    Article  CAS  Google Scholar 

  16. Ji, Y. et al. Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nat. Immunol. 12, 1230–1237 (2011).

    Article  CAS  Google Scholar 

  17. Gattinoni, L. et al. A human memory T cell subset with stem cell-like properties. Nat. Med. 17, 1290–1297 (2011).

    Article  CAS  Google Scholar 

  18. Bender, T. P., Kremer, C. S., Kraus, M., Buch, T. & Rajewsky, K. Critical functions for c-Myb at three checkpoints during thymocyte development. Nat. Immunol. 5, 721–729 (2004).

    Article  CAS  Google Scholar 

  19. Dias, S. et al. Effector regulatory T cell differentiation and immune homeostasis depend on the transcription factor Myb. Immunity 46, 78–91 (2017).

    Article  CAS  Google Scholar 

  20. Ramsay, R. G. & Gonda, T. J. MYB function in normal and cancer cells. Nat. Rev. Cancer 8, 523–534 (2008).

    Article  CAS  Google Scholar 

  21. Greig, K. T., Carotta, S. & Nutt, S. L. Critical roles for c-Myb in hematopoietic progenitor cells. Semin. Immunol. 20, 247–256 (2008).

    Article  CAS  Google Scholar 

  22. Ji, Y. et al. Identification of the genomic insertion site of Pmel-1 TCR α and β transgenes by next-generation sequencing. PLoS ONE 9, e96650 (2014).

    Article  Google Scholar 

  23. Seibler, J. et al. Rapid generation of inducible mouse mutants. Nucleic Acids Res. 31, e12 (2003).

    Article  Google Scholar 

  24. Yuan, J., Crittenden, R. B. & Bender, T. P. c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-xL. J. Immunol. 184, 2793–2804 (2010).

    Article  CAS  Google Scholar 

  25. Jenkins, M. K. & Moon, J. J. The role of naive T cell precursor frequency and recruitment in dictating immune response magnitude. J. Immunol. 188, 4135–4140 (2012).

    Article  CAS  Google Scholar 

  26. Appay, V., van Lier, R. A., Sallusto, F. & Roederer, M. Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry. A. 73, 975–983 (2008).

    Article  Google Scholar 

  27. van der Windt, G. J. et al. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36, 68–78 (2012).

    Article  CAS  Google Scholar 

  28. Zhao, L. et al. Integrated genome-wide chromatin occupancy and expression analyses identify key myeloid pro-differentiation transcription factors repressed by Myb. Nucleic Acids Res. 39, 4664–4679 (2011).

    Article  CAS  Google Scholar 

  29. Taylor, D., Badiani, P. & Weston, K. A dominant interfering Myb mutant causes apoptosis in T cells. Genes Dev. 10, 2732–2744 (1996).

    Article  CAS  Google Scholar 

  30. Salomoni, P., Perrotti, D., Martinez, R., Franceschi, C. & Calabretta, B. Resistance to apoptosis in CTLL-2 cells constitutively expressing c-Myb is associated with induction of BCL-2 expression and Myb-dependent regulation of bcl-2 promoter activity. Proc. Natl Acad. Sci. USA 94, 3296–3301 (1997).

    Article  CAS  Google Scholar 

  31. Omilusik, K. D. et al. Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. J. Exp. Med. 212, 2027–2039 (2015).

    Article  Google Scholar 

  32. Dominguez, C. X. et al. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. J. Exp. Med. 212, 2041–2056 (2015).

    Article  CAS  Google Scholar 

  33. Boudousquie, C. et al. Differences in the transduction of canonical Wnt signals demarcate effector and memory CD8 T cells with distinct recall proliferation capacity. J. Immunol. 193, 2784–2791 (2014).

    Article  CAS  Google Scholar 

  34. Sandberg, M. L. et al. c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation. Dev. Cell. 8, 153–166 (2005).

    Article  CAS  Google Scholar 

  35. Gattinoni, L. et al. Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells. J. Clin. Invest. 115, 1616–1626 (2005).

    Article  CAS  Google Scholar 

  36. Wirth, T. C. et al. Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8+ T cell differentiation. Immunity 33, 128–140 (2010).

    Article  CAS  Google Scholar 

  37. Klebanoff, C. A. et al. Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in mice. Clinical Cancer Res. 17, 5343–5352 (2011).

    Article  CAS  Google Scholar 

  38. Chen, Z. et al. miR-150 regulates memory CD8 T cell differentiation via c-Myb. Cell Reports 20, 2584–2597 (2017).

    Article  CAS  Google Scholar 

  39. Im, S. J. et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417–421 (2016).

    Article  CAS  Google Scholar 

  40. Wu, T. et al. The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci Immunol. 1, eaai8593 (2016).

    Article  Google Scholar 

  41. Utzschneider, D. T. et al. T cell factor 1-expressing memory-like CD8+ T cells sustain the immune response to chronic viral infections. Immunity 45, 415–427 (2016).

    Article  CAS  Google Scholar 

  42. Brummelman, J. et al. High-dimensional single cell analysis identifies stem-like cytotoxic CD8+ T cells infiltrating human tumors. J. Exp. Med. 215, 2520–2535 (2018).

    Article  CAS  Google Scholar 

  43. Mizuguchi, G. et al. c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter. J. Biol. Chem. 270, 9384–9389 (1995).

    Article  CAS  Google Scholar 

  44. Reddy, M. A. et al. Opposing actions of c-ets/PU.1 and c-myb protooncogene products in regulating the macrophage-specific promoters of the human and mouse colony-stimulating factor-1 receptor (c-fms) genes. J. Exp. Med. 180, 2309–2319 (1994).

    Article  CAS  Google Scholar 

  45. Peng, S., Lalani, S., Leavenworth, J. W., Ho, I. C. & Pauza, M. E. c-Maf interacts with c-Myb to down-regulate Bcl-2 expression and increase apoptosis in peripheral CD4 cells. Eur. J. Immunol. 37, 2868–2880 (2007).

    Article  CAS  Google Scholar 

  46. Dash, A. B., Orrico, F. C. & Ness, S. A. The EVES motif mediates both intermolecular and intramolecular regulation of c-Myb. Genes Dev. 10, 1858–1869 (1996).

    Article  CAS  Google Scholar 

  47. Yang, J. et al. Identification of p100 as a coactivator for STAT6 that bridges STAT6 with RNA polymerase II. EMBO J. 21, 4950–4958 (2002).

    Article  CAS  Google Scholar 

  48. Crompton, J. G., Sukumar, M. & Restifo, N. P. Uncoupling T-cell expansion from effector differentiation in cell-based immunotherapy. Immunol. Rev. 257, 264–276 (2014).

    Article  CAS  Google Scholar 

  49. Gattinoni, L. et al. Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells. Nat. Med. 15, 808–813 (2009).

    Article  CAS  Google Scholar 

  50. Sabatino, M. et al. Generation of clinical-grade CD19-specific CAR-modified CD8+ memory stem cells for the treatment of human B-cell malignancies. Blood 128, 519–528 (2016).

    Article  CAS  Google Scholar 

  51. Yang, Q. et al. TCF-1 upregulation identifies early innate lymphoid progenitors in the bone marrow. Nat. Immunol. 16, 1044–1050 (2015).

    Article  CAS  Google Scholar 

  52. Eil, R. et al. Ionic immune suppression within the tumour microenvironment limits T cell effector function. Nature 537, 539–543 (2016).

    Article  CAS  Google Scholar 

  53. Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome. Biol. 14, R36 (2013).

    Article  Google Scholar 

  54. Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome. Biol. 15, 550 (2014).

    Article  Google Scholar 

  55. Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).

    Article  CAS  Google Scholar 

  56. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545–15550 (2005).

    Article  CAS  Google Scholar 

  57. Roychoudhuri, R. et al. Transcriptional profiles reveal a stepwise developmental program of memory CD8+ T cell differentiation. Vaccine 33, 914–923 (2015).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research (ZIABC011480) (to L.G.); the US National Institutes of Health grants (GM100776 and CA85842) (to T.P.B.); the Wellcome Trust/Royal Society (105663/Z/14/Z), the UK Biotechnology and Biological Sciences Research Council (BB/N007794/1) and Cancer Research UK (C52623/A22597) (to R.R.). We thank K. Hanada for providing B16 (H-2b)-hgp100. This work used the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov).

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Authors

Contributions

S.G., J.F., J.B.L, P.B., N.E.L., J.H., J.D.H., N.V.H., V.K., W.G.T., D.G., R.R. and Y.J. performed the experiments. S.G., W.Z., J.B.L., Y.J. and L.G. analyzed the experiments. S.G., B.W.H., R.R., N.P.R., T.P.B. and L.G. designed the experiments. Z.Y., H.H.X., A.B. and T.P.B. contributed reagents. W.Z., J.B.L., R.R., N.P.R., T.P.B. and Y.J. edited the manuscript. S.G. and L.G wrote the manuscript.

Corresponding author

Correspondence to Luca Gattinoni.

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Competing interests

P.B. and B.W.H. are full-time employees of MedImmune and have stock in AstraZeneca. S.G., Y.J. and L.G. have a pending patent on c-Myb technology.

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Integrated supplementary information

Supplementary Figure 1 c-Myb-deficient CD8+ T cells display a more pronounced contraction.

(a,b) Flow cytometry of splenic CD8+ T cells (a) and percentage of pmel-1 T cells (b) in the lymph nodes (LN) after transfer of 105 pmel-1 Thy1.1 Mybfl/fl or pmel-1 Thy1.1 Myb∆/∆ CD8+ T cells into wild-type mice infected with gp100-VV, assessed 5d and 10d after infection (n = 3 mice per group). (c,d) Flow cytometry of splenic CD8+ T cells (c) and percentage (d) of pmel-1 T cells in the lung after transfer as described in a,b. Data are representative of two independent experiments. Data are shown after gating on live, CD8+ T cells (a, c). Data in b and d are shown as the mean ± s.e.m.; shapes represent individual mice. **= P < 0.01; ns, not significant (unpaired two-tailed Student’s t-test).

Supplementary Figure 2 c-Myb-deficient CD8+ T cells exhibit defects in survival but not in proliferation.

(a, b) Flow cytometry (a) and percentage (b) of BrdU incorporation into pmel-1 T cells 3d and 5d after transfer of 105 pmel-1 Thy1.1 Myb+/+ or pmel-1 Thy1.1 Myb∆/∆ CD8+ T cells into wild-type mice infected with gp100-VV (n = 3 mice per group). (c, d) Flow cytometry (c) and percentage (d) of Annexin V+ pmel-1 T cells 3d and 5d after adoptive transfer as described in a,b. Data are representative of two independent experiments. Data are shown after gating on live CD8+ Thy1.1+ cells (a) and CD8+ Thy1.1+ (c). Data in b and d are shown as the mean ± s.e.m.; shapes represent individual mice. **= P < 0.01; ns, not significant (unpaired two-tailed Student’s t-test).

Supplementary Figure 3 c-Myb-deficient CD8+ T cells are prone to terminal differentiation.

(a) Flow cytometry of pmel-1 T cells in the lymph nodes (LN) 5d after transfer of 105 pmel-1 Thy1.1 Mybfl/fl or pmel-1 Thy1.1 Myb∆/∆ CD8+ T cells into wild-type mice infected with gp100-VV (n = 3 mice per group). (b) Percentage of KLRG1+ CD62L (left) and KLRG1 CD62L+ (right) pmel-1 T cells in the LN 5d after transfer as in a. (c) Flow cytometry of pmel-1 T cells in the lung 5d after transfer as in a. (d) Percentage of KLRG1+ CD62L (left) and KLRG1 CD62L+ (right) pmel-1 T cells in the lung 5d after transfer as in a. Data are representative of two independent experiments. Data are shown after gating on live CD8+ Thy1.1+ cells (a, c). Data in b and d are shown as the mean ± s.e.m.; shapes represent individual mice. **= P < 0.01; ****= P < 0.0001 (unpaired two-tailed Student’s t-test).

Supplementary Figure 4 c-Myb influences mitochondrial respiration irrespective of its impact on differentiation.

(a) Oxygen consumption rate (OCR) of CD44+CD62L+ pmel-1 Myb+/+ and pmel-1 Myb∆/∆ CD8+ T cells activated in vitro with anti-CD3 and anti-CD28 antibodies in the presence of IL-2, assessed on d5 after activation. Data are shown under basal conditions and in response to the indicated molecules (n = 5 technical replicates per time point). FCCP, Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; Eto, Etomoxir; Ant, Antimycin; Rot, Rotenone. (b, c) SRC (b) and Reduction of OCR after Etomoxir administration (c) of pmel-1 Myb+/+ and pmel-1 Myb∆/∆ CD8+ T cells generated as in a. SRC, spare respiratory capacity. (n = 3 time points per condition, each data point is the average of 5 technical replicates) (c). Data are representative of two independent experiments. Data are shown as the mean ± s.e.m.; shapes represent technical repeats. *= P < 0.05; ***= P < 0.001; (unpaired two-tailed Student’s t-test).

Supplementary Figure 5 c-Myb is critical for secondary and long-term memory.

(a, c) Flow cytometry of pmel-1 T cells in the lungs (a) and lymph nodes (c) after transfer of 3☓105 pmel-1 Thy1.1 Mybfl/fl CD8+ T or pmel-1 Thy1.1 Myb∆/∆ CD8+ T cells, assessed 90d after infection with gp100-VV (n = 3 mice per group). (b, d) Numbers of pmel-1 T cells in the lungs and lymph nodes assessed 90d after infection as described in a, c. (e, g) Flow cytometry of pmel-1 T cells in the lungs (e) and lymph nodes (g) assessed 30d after the transfer of 5☓104 pmel-1 Thy1.1 Mybfl/fl or pmel-1 Thy1.1 Myb∆/∆ primary memory CD8+ T cells followed by secondary infection with gp100-adV (n = 3 mice per group). (f, h) Numbers of pmel-1 T cells in the lung and lymph nodes assessed 30d after secondary infection as described in e. Data are shown after gating on live CD8+ (a, c, e, g). Data in b, d, f and h are shown as the mean ± s.e.m.; shapes represent individual mouse (b, d, f and h) *= P < 0.05, ***= P < 0.001 (unpaired two-tailed Student’s t-test).

Supplementary Figure 6 c-Myb-deficient CD8+ T cells are enriched with genes found in IL-7rlow effector cells.

(a) Flow cytometry of pmel-1 T cells pre and post-sorting. Cells were isolated 5d after transfer of 3 × 105 pmel-1 Myb+/+ or pmel-1 Myb∆/∆ CD8+ T cells into wild-type mice infected with gp100-VV. (b) Gene-Set Enrichment Assay (GSEA) showing positive enrichment of genes upregulated in IL-7rlow (left) and negative enrichment of genes upregulated in IL-7-rhigh (right) in pmel-1 Myb∆/∆ CD8+ T cells obtained as described in a (n = 3, each from 2 pooled mice per group). (c) Quantitative RT-PCR of Bach2, Prdm1, Eomes and Tbx21 mRNA in pmel-1 CD8+ T cells sorted 5d after transfer of 105 pmel-1 Myb+/+ CD8+ T cells or pmel-1 Myb∆/∆ CD8+ T cells into wild-type mice infected with gp100-VV. Results are presented relative to Rpl13 (n = 3 technical replicates). Data (c) are representative of two independent experiments. Data are shown after gating on live CD8+ Thy1.1+ cells (a). Data in c are shown as the mean ± s.e.m.; shapes represent individual technical replicates *= P < 0.05, **= P < 0.01, ***= P < 0.001 and ****= P < 0.0001; ns, non-significant (unpaired two-tailed Student’s t-test).

Supplementary Figure 7 Overexpression of c-Myb enhances the formation of stem cell-like memory TCM cells.

(a,b) Flow cytometry of splenic CD8+ T cells (a) and percentage of pmel-1 T cells (b) in the lung 5d and 32d after co-transfer of 5 × 104 pmel-1 Thy1.1 and 5 × 104 pmel-1 Myb-Thy1.1 Ly5.1 CD8+ T cells into wild-type mice infected with gp100-VV (n = 3 mice per group per time point). (c,d) Flow cytometry of splenic CD8+ T cells (c) and percentage of pmel-1 T cells (d) in the lymph nodes (LN) 5d and 32d after adoptive co-transfer as described in a,b. (e,f) Flow cytometry of pmel-1 T cells in the lung (e) and LN (f) 5d and 32d after co-transfer as described in a,b. Data are representative of two independent experiments. Data are shown after gating on live CD8+ cells (a,c), and live, CD8+ Thy1.1+Ly5.1+ or CD8+ Thy1.1+Ly5.1 cells (e, f). Data in b and d are shown as the mean ± s.e.m.; shapes represent individual mice.*= P < 0.05, **= P < 0.01; ns, non-significant (unpaired two-tailed Student’s t-test).

Supplementary Figure 8 Myb overexpression enhances long-term memory in mice after tumor eradication.

(a,b) Flow cytometry of splenocytes (a) and percentage of pmel-1 T cells (b) in the lymph nodes 470d after transfer of 5 × 106 pmel-1 Ly5.2 Thy1.1 and pmel-1 Myb-Thy1.1 Ly5.2 CD8+ T cells into Ly5.1 mice bearing B16-hgp100 melanoma in conjunction with gp100-VV and IL-2. (c) Flow cytometry of pmel-1 T cells in lymph nodes 470d after transfer as described in a. (d) Combinatorial cytokine production by splenic pmel-1 T cells 470d after transfer as described in a. Data are shown after gating on live cells (a), and live, CD8+ Ly5.2+ cells (c). Data in b are shown as the mean±s.e.m.; shapes represent individual mice.

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Gautam, S., Fioravanti, J., Zhu, W. et al. The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity. Nat Immunol 20, 337–349 (2019). https://doi.org/10.1038/s41590-018-0311-z

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