Cancer therapy: Tumours switch to resist

Abstract

Tumour cells can respond to targeted immune-cell therapies by losing proteins that mark them as being cancerous. Subverting this resistance mechanism may lead to more durable cancer-treatment strategies.

Figure 1. Escape by dedifferentiation

Cancer cells express certain antigens that are not expressed by non-cancerous cells (red colour on cells indicates antigen expression). Adoptive cell transfer is a type of immunotherapy in which immune cells called T cells with receptors that specifically recognize these defining antigens are transferred into patients, where they initiate an immune response that kills the cancer cells. Landsberg et al. show that, in the process of cancer-cell killing, the tumour-infiltrating T cells release the inflammatory molecule TNF-α, which causes some of the tumour cells to stop expressing of some of their cancer-specific antigens. These ‘dedifferentiated’ cancer cells are no longer recognized by the T cells, resulting in resistance to the therapy and tumour regrowth.