New research finds the culprit of T cell failure in cancer

Although immunocheckpoint blocking therapy has significantly changed the situation of cancer treatment and has clinical effect in cancer treatment, not all tumors respond to this immunotherapy Resistance to treatment, which occurs in a variety of cancers, largely hinders this strategy In a new study, microsatellite instability was found in two different types of colorectal cancer MSI CRC and microsatellite are resistant to PD-1 central therapy Stable, MSS) colorectal cancer (hereinafter referred to as MSS CRC) - T cell failure They found that tumor infiltrating T cells failed in both types of colorectal cancer The difference is that MSS T cell failure in CRC is driven by VEGF-A, but MSI T cell failure in CRC is not the case Relevant research results were published in the Journal of science immunology on November 8, 2019, with the title of "VEGF-A" drives TOX-dependent T cell exhaustion in anti–PD-1–resistant microsatellite stable colorectal cancers”。 The researchers report that VEGF-A induces the expression of transcription factor tox in T cells, thereby activating failure specific transcription programs in these cells By using in vitro, in vitro and in vivo mouse studies, they confirmed that blocking PD-1 and VEGF-A together can restore the anti-tumor function of T cells, making MSS CRC sensitive to PD-1 blocking therapy, so as to better control the tumor of MSS CRC.