Immune cells track hard-to-target brain tumours

Abstract

Clinical trials reveal that personalized vaccines can boost immune-cell responses to brain tumours that don’t usually respond to immunotherapy. The findings also point to how to improve such treatments.

Keywords: Cancer; Immunology.

Figure 1 |. Using immunotherapy to target human brain tumours.

Keskin et al. and Hilf et al. report the outcomes of phase I clinical trials that tested ways of boosting immune responses against glioblastoma tumours, which are hard to target with immunotherapy. Both authors tried to enhance immune responses against tumour-specific, mutant versions of proteins, termed neoantigens, that are displayed by being bound to receptors on a person’s tumour cells. Keskin et al. gave participants vaccines consisting of personalized sets of peptides (protein fragments) that matched the amino-acid sequences of their specific neoantigens. Hilf et al. combined such a personalized vaccine with one that targets non-mutant proteins common to this type of tumour (not shown). Both papers report that vaccination boosted immune responses involving CD8⁺ T cells and CD4⁺ T cells that recognized the neoantigens. However, this did not prevent cancer-associated death. Perhaps this is because T cells entered a dysfunctional state termed exhaustion, as reported by Keskin and colleagues. Entry into this state can be mediated by a T-cell-receptor protein called PD-1. Perhaps future studies will test whether blocking exhaustion by using antibodies that target PD-1 might enable such tumour-targeting T cells to remain active and secrete the cytokine molecules that aid tumour-cell destruction.