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SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling

Bao Zhao1,2, Weipeng Gong1, Anjun Ma3

  • 1Department of Microbial Infection and Immunity, Infectious Disease Institute, The Ohio State University, Columbus, OH, USA.

Nature Immunology
|October 20, 2022
PubMed

Insights

SUSD2 negatively regulates CD8+ T cell antitumor immunity by blocking IL-2 binding. Removing SUSD2 enhances T cell function, blunts tumor growth, and shows potential for cancer immunotherapy.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Dysfunctional CD8+ T cells contribute to tumor immunosuppression.
  • Identifying regulators of CD8+ T cell function is crucial for cancer immunotherapy.

Purpose of the Study:

  • To investigate the role of SUSD2 in regulating CD8+ T cell antitumor function.
  • To explore SUSD2 as a potential target for cancer immunotherapy.

Main Methods:

  • Utilized knockout mouse models (Susd2-/-) to assess CD8+ T cell function.
  • Employed quantitative mass spectrometry to identify protein interactions.
  • Analyzed the effect of SUSD2 on IL-2 receptor alpha binding and T cell effector molecule production.

Main Results:

  • SUSD2 acts as a negative regulator of CD8+ T cell antitumor function.
  • Susd2-/- CD8+ T cells exhibited enhanced effector molecule production and suppressed tumor growth.
  • SUSD2 interacts with IL-2 receptor alpha, inhibiting IL-2 binding and subsequent T cell activation.
  • SUSD2 did not impact regulatory CD4+ T cell function.
  • Adoptive transfer of Susd2-/- chimeric antigen receptor T cells demonstrated potent antitumor responses.

Conclusions:

  • SUSD2 is a key negative regulator of CD8+ T cell-mediated antitumor immunity.
  • Targeting SUSD2 offers a promising strategy for enhancing cancer immunotherapy efficacy.

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