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Chemotherapy brings virtual memory T cells into reality for cancer therapy

Cellular & Molecular Immunology volume 18, pages 1339–1340 (2021)Cite this article

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The anticancer effect of chemotherapy has been historically attributed to directly inducing proliferating cancer cell death.1 Accumulating evidence suggests that chemotherapy also engages the immune system. Some chemotherapies can induce immunogenic cell death, leading to tumor antigen uptake and presentation by dendritic cells to activate tumor-reactive T cells.2 A new study by Wang et al. adds another dimension to this paradigm by demonstrating that chemotherapy pretreatment of cancer cells can directly activate virtual memory (VM) CD8+ T cells to mediate tumor cytotoxicity in an antigen-independent manner.3

During T-cell development in the thymus, CD8+ T cells with a heightened reactivity to self-peptide/MHC complexes express the transcription factor Eomes and differentiate into VM T cells in the periphery following IL-15 cytokine signaling.4,5,6 Phenotypically, murine VM T cells are CD8+TCRα/β+CD44highCD122+CD49dlow and, upon exposure to the cytokines IL-12 and IL-18, produce granzyme B and IFNγ independent of TCR signaling.4,5,7 This antigen independence facilitates VM T-cell participation in bystander killing, which may help control early stages of infection or possibly mitigate tumor growth.4,5,8

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Acknowledgements

Figure 1 was created using biorender.com, with the help of Meagan Rollins.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, 55414, MN, USA

    Zoe C. Schmiechen, Adam L. Burrack & Ingunn M. Stromnes

  2. Center for Immunology, University of Minnesota Medical School, Minneapolis, 55414, MN, USA

    Zoe C. Schmiechen, Adam L. Burrack & Ingunn M. Stromnes

  3. Center for Genome Engineering, University of Minnesota Medical School, Minneapolis, 55414, MN, USA

    Ingunn M. Stromnes

  4. Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, 55414, MN, USA

    Ingunn M. Stromnes

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  1. Zoe C. Schmiechen
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  2. Adam L. Burrack
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Correspondence to Ingunn M. Stromnes.

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Schmiechen, Z.C., Burrack, A.L. & Stromnes, I.M. Chemotherapy brings virtual memory T cells into reality for cancer therapy. Cell Mol Immunol 18, 1339–1340 (2021). https://doi.org/10.1038/s41423-020-0496-6

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