Abstract

Immune checkpoint inhibitors (ICI) are a class of anti-cancer drugs that work by potentiating the patient’s immune response. ICI delivered impressive clinical benefits in cancer types previously considered untreatable, such as metastatic melanoma. Unfortunately, only some patients respond to this type of immunotherapy, for reasons that remain substantially unknown. Despite our incomplete understanding of this phenomenon, it has been observed that the presence of certain cell types might characterize immunotherapy-responsive tumours. For instance, infiltration of immune cells (i.e. T and B cells) has been associated with an increased probability of ICI response. On the other hand, an abundance of stromal cells (i.e. cancer-associated fibroblasts, or CAFs) has been associated with a lack of response and poor clinical outcomes. As a consequence, targeting CAFs has been proposed as a possible strategy to increase the efficacy of cancer immunotherapy. Surprisingly, we recently identified a subpopulation of CAFs associated with ICI response independently of T and B cells. This observation might help to identify ICI responsive tumours and has important consequences for therapeutic strategies targeting fibroblasts in cancer immunotherapy.