Editors' ChoiceCancer Immunotherapy

New connections: Stimulating immune memory against cancer

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Sci. Signal.  02 Jan 2018:
Vol. 11, Issue 511, eaar8122
DOI: 10.1126/scisignal.aar8122

Future immunotherapies may stimulate immune system attack as well as memory against cancer to prevent relapse in patients.

Cancer immunotherapy stimulates the patient’s immune system to attack tumor cells. Although promising, its success has been limited. We are just beginning to understand the many cell types of the immune system and how they interact with the tumor and with each other, such as how regulatory T cells (Tregs) can counteract immunostimulatory drugs, such that we may develop better immunotherapeutics. But beyond the primary tumor, relapse (tumor regrowth) is an ever-present concern for cancer patients long after treatment. Two studies reveal strategies that stimulate immune attack as well as memory against cancers in animal models and, hence, may be developed to prevent relapse in patients.

In this issue of Science Signaling, Nie et al. show that co-inhibiting a receptor for tumor necrosis factor (TNF) reduced Treg activation and shrank colon and breast tumors in mice that were unresponsive to common single-agent immunotherapies. Moreover, the then tumor-free mice were resistant to rechallenge with the same cancer cells. The findings suggest that the efficacy of immunotherapy may be improved by the addition of anti-TNF therapeutics (see also the Review by Vanamee and Faustman). In the Archives, Gumbleton et al. uncovered a way to prevent a common pitfall of current immunotherapy—immune cell exhaustion—as well as establish antitumor immune memory. They found that a pulsatile regimen that inhibited the phosphatase SHIP1 not only durably enhanced the antitumor activity of critical populations of immune cells and increased the survival of mice with lymphoma and colon cancer but also induced immunological memory against the tumor cells. The caveats of animal models aside, these reports reveal potential clinical strategies that may increase and broaden the efficacy of immunotherapy, with a greater hope for relapse-free outcomes in cancer patients.

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