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Cancer

IL-2 engineered MSCs rescue T cells in tumours

Nature Cell Biology volume 24, pages 1689–1691 (2022)Cite this article

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IL-2 is a powerful growth factor for T cells. New work shows that immune checkpoint blockade depends upon the presence of IL-2, and that mesenchymal stem cells can be efficiently engineered to safely deliver it directly in advanced tumours to rescue CD8+ T cell responsiveness to anti-PD-L1 antibody treatment.

Cytolytic T cells have a critical role in tumour control through their specific recognition and killing of transformed cells, and most immunotherapies, including immune checkpoint blockade (ICB), function by reinvigorating them1. However, the tumour microenvironment (TME) is hostile to T cells, and only a limited proportion of patients respond to ICB. For example, the TME is typically deprived of sufficient nutrients, oxygen and co-stimulatory signals needed for the full biological activities of T cells. Interleukin-2 (IL-2), also known as the T cell growth factor, is a pleiotropic and potent cytokine that is crucial for T cell proliferation, differentiation and homeostasis2. Notably, systemically administered IL-2, although toxic, having a short half-life and demonstrated to expand regulatory T (Treg) cells, is considered the first effective immunotherapy. Indeed, IL-2 can confer durable, complete and apparently curative regressions in some patients with metastatic melanoma and renal cancer3. In this issue of Nature Cell Biology, Bae et al.4 begin with a simple but fundamental question that has not been previously directly addressed: is the presence of IL-2 within the TME required for responsiveness to ICB? In addition, they sought to determine whether exogenous IL-2 can overcome resistance to ICB, as well as to evaluate whether targeted delivery of IL-2 by engineered mesenchymal stem cells (MSCs) can alleviate toxicity, improve local and distal tumour control, and synergize with chemotherapy.

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Fig. 1: Intratumoural delivery of SIL2 by EMSCs rejuvenates pre-existing CD8+ TILs to control tumours.

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Authors and Affiliations

  1. Department of Oncology, Ludwig Institute for Cancer Research Lausanne, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

    Melita Irving, Yaquelin Ortiz-Miranda & George Coukos

Authors
  1. Melita Irving
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  2. Yaquelin Ortiz-Miranda
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  3. George Coukos
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Correspondence to George Coukos.

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Competing interests

G.C. has received grants or research support from, or is coinvestigator in clinical trials by, Bristol-Myers Squibb, Celgene, Boehringer Ingelheim, Roche, Tigen Pharma, Iovance and Kite. The Lausanne University Hospital (CHUV) has received honoraria for advisory services G.C. has provided to AstraZeneca AG, Bristol-Myers Squibb SA, F. Hoffmann-La Roche AG, MSD Merck AG and Geneos Therapeutics. G.C. has patents in the domain of antibodies and vaccines targeting the tumour vasculature as well as technologies related to T cell expansion and engineering for T cell therapy. G.C. has received royalties from the University of Pennsylvania. The three co-authors are included in an intellectual property filing regarding an IL-2 variant.

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Irving, M., Ortiz-Miranda, Y. & Coukos, G. IL-2 engineered MSCs rescue T cells in tumours. Nat Cell Biol 24, 1689–1691 (2022). https://doi.org/10.1038/s41556-022-01029-0

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