Pathogenesis and treatment of mature T cell tumors

Mature T-cell tumors, such as non-Hodgkin T-cell lymphoma, are highly invasive and drug-resistant, and patients often have a poor prognosis. Recently, “Nature” series of two articles published a new interpretation of the pathogenesis of non-Hodgkin’s T-cell lymphoma, thus providing a new direction for the effective development of new therapies for this type of malignant lymphoma.

In the first study, the Wartewig team used the fusion protein ITK-SYK to construct a transgenic mouse model of late-onset T-cell lymphoma (Nature. Doi: 10.1038 / nature24649), and found that the single or double copy of the PDCD1 gene encoding the PD1 protein was deleted. T cell lymphoma undergoes rapid malignant transformation and accelerates the death of the mouse model. In addition, the application of PD1 or PD-L1 inhibitors can produce similar effects. The related mechanism is that PD1 up-regulates PTEN expression and inhibits the tumor malignant proliferation pathway PI3K.

In another article, Maciocia et al. Applied chimeric antigen receptor T cell immunotherapy (CAR-T) therapy (Nat Med. Doi: 10.1038 / nm.4444) to construct CAR-T cells that specifically target TRBC1 but not TRBC2 To treat TRBC1-positive T-cell carcinoma. While killing tumor cells, leaving enough T cells to fight infection. The clinical trial of this method will be officially launched in 2018.

Nature senior editor Megan Cully said that the above-mentioned important findings provide a new treatment strategy for the treatment of mature T-cell malignancies and warn that these tumors are not suitable for treatment with PD1 or PDL1 inhibitors.