Fighting cancer by targeting immune cells

Fighting cancer by targeting immune cells: How antibodies against integrins block immunosuppression by Tregs

Tumor cells can be recognized, killed and eliminated by immune cells. Progression of cancer in patients is due in part to the failure of this defense mechanism, often caused by undue suppression of anti-tumor immune responses. Important culprits of immunosuppression in tumors are regulatory T cells, or Tregs. These cells are specialized in suppressing immune responses. They are indispensable to protect us from excessive, auto-destructive reactions that can cause autoimmune diseases. But in cancer, Tregs play deleterious roles by suppressing anti-tumor immunity.

How Tregs actually suppress other immune cells is still incompletely understood. Two years ago, we discovered an important mechanism of immunosuppression by Tregs. It implies release of the TGF-β1 cytokine, a protein messenger that transmits inhibitory signals from Tregs to other immune cells. TGF-β1 is released from molecular complexes that contain protein GARP and are located on the Treg surface. In our most recent work, published this week in PNAS, we show that the release of TGF-β1 from GARP-containing complexes requires yet another surface protein, called integrin αVβ8. We used antibodies as potential therapeutic tools to block the β8 moiety of integrin αVβ8, and showed that anti-β8 antibodies reduce TGF-β1 release and immunosuppression by human Tregs. This work suggests that anti-β8 antibodies blocking Treg-mediated immunosuppression could boost anti-tumor immune responses and thus serve as a novel approach for the immunotherapy of cancer.

Article describing this research

Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVβ8.

Stockis J, Liénart S, Colau D, Collignon A, Nishimura SL, Sheppard D, Coulie PG, Lucas S.

Proc Natl Acad Sci U S A. (2017), pii: 201710680.