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Recent advances in basic science
Emerging interleukin targets in the tumour microenvironment: implications for the treatment of gastrointestinal tumours
  1. Lindsay Kathleen Dickerson1,
  2. Jason A Carter1,
  3. Karan Kohli1,2,
  4. Venu G Pillarisetty1
  1. 1 Hepatopancreatobiliary Surgery, University of Washington, Seattle, Washington, USA
  2. 2 Flatiron Bio, Palo Alto, California, USA
  1. Correspondence to Dr Venu G Pillarisetty, Hepatopancreatobiliary Surgery, University of Washington, Seattle, WA 98195, USA; vgp{at}uw.edu

Abstract

The effectiveness of antitumour immunity is dependent on intricate cytokine networks. Interleukins (ILs) are important mediators of complex interactions within the tumour microenvironment, including regulation of tumour-infiltrating lymphocyte proliferation, differentiation, migration and activation. Our evolving and increasingly nuanced understanding of the cell type-specific and heterogeneous effects of IL signalling has presented unique opportunities to fine-tune elaborate IL networks and engineer new targeted immunotherapeutics. In this review, we provide a primer for clinicians on the challenges and potential of IL-based treatment. We specifically detail the roles of IL-2, IL-10, IL-12 and IL-15 in shaping the tumour-immune landscape of gastrointestinal malignancies, paying particular attention to promising preclinical findings, early-stage clinical research and innovative therapeutic approaches that may properly place ILs to the forefront of immunotherapy regimens.

  • CYTOKINES
  • IMMUNOTHERAPY
  • INTERLEUKINS
  • GASTROINTESTINAL CANCER
  • CANCER IMMUNOBIOLOGY

http://dx.doi.org/10.1136/gutjnl-2023-329650

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    Footnotes

    • LKD and JAC are joint first authors.

    • Twitter @Karan_Immunoonc, @pancsurg

    • Contributors Conceptualisation—LKD, JAC, KK and VGP. Literature review—LKD, JAC and KK. Writing (original draft)—LKD, JAC and KK. Writing (review and editing)—LKD, JAC and VGP. Figures (creation)—LKD. Figures (editing)—LKD, JAC and VGP. Review/approval of final manuscript—LKD, JAC, KK and VGP. Guarantor—LKD and VGP.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Disclaimer The funders had no role in the conceptualisation, decision to publish or preparation of this manuscript.

    • Competing interests VGP is a member of the scientific advisory board for TriSalus Life Sciences. He has served as a consultant for GlaxoSmithKline in 2019, Imvax in 2019, Takeda in 2020, and Umoja and Sensei in 2022. He has had research funding from AstraZeneca, Ipsen, Merck, NGM and OncoResponse.

    • Provenance and peer review Commissioned; externally peer reviewed.