Editors' ChoiceCancer Immunotherapy

Highlight: Antitumor strategies

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Sci. Signal.  10 Oct 2017:
Vol. 10, Issue 500, eaaq1397
DOI: 10.1126/scisignal.aaq1397

Two papers highlight potential ways to boost the antitumor immune response.

Although great advances have been made in the manipulation of the immune system to target tumors, major challenges remain, including how best to stimulate the antitumor activity of immune cells. T helper 9 (TH9) cells, a subset of CD4+ T cells that secrete the cytokines interleukin-9 (IL-9) and IL-21, have potent antitumor activity in vivo because of their ability to stimulate cytotoxic T cells. Bi et al. found that if naïve CD4+ T cells were differentiated into TH9 cells in vitro in the presence of the cytokine IL-7, the cells produced more IL-9 and IL-21 and had enhanced antitumor activity in mice. These data suggest that IL-7–treated TH9 cells could have potential as an effective cellular therapy against cancer. In a different approach, Gumbleton et al. sought to enhance immune cell activity by targeting an endogenous inhibitor, the phosphatase SHIP1. T cell signaling is inhibited by SHIP1 through its dephosphorylation of critical signaling proteins. However, complete inhibition or loss of SHIP1 counterintuitively leads to immune cell exhaustion; an inability to mount an immune response. Gumbleton et al. found that intermittent treatment with a SHIP1 inhibitor was sufficient to enhance the antitumor activity of immune cells in mouse models of lymphoma and colon cancer without causing exhaustion. Furthermore, this treatment strategy also induced immunological memory against the tumor cells. Together, these data suggest that antitumor immune responses can be boosted by targeting both stimulatory and inhibitory mechanisms.

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