Horn, et al. – Summary
Horn S, Leonardelli S, Sucker A, Schadendorf D, Griewank KG, Paschen A. Tumor CDKN2A-Associated JAK2 Loss and Susceptibility to Immunotherapy Resistance. J Natl Cancer Inst. 2018 Jun 1;110(6):677-681. Available at: https://academic.oup.com/jnci/article/110/6/677/4780396
Patients with advanced melanoma treated with different types of immunotherapies in order to activate the immune system against the tumor. Nevertheless, in the majority of patients, melanomas are not responding to therapy, and the underlying mechanisms are still poorly understood. Immunotherapy exploits the capacity of T cells to kill tumor cells. Besides other mechanisms tumor cell killing is induced by T cell-derived IFNγ, i.e. IFNy signaling in tumor cells can induce apoptosis. In this study we asked if tumor cells have particular genetic defects involved in resistance to IFNy. We focused on chromosomal alterations and observed that melanoma cells frequently show larger deletions in one of the two copies of chromosome 9 and these deletions generally affects two genes: CDKN2A, a tumor suppressor, and JAK2, involved in IFNγ signaling. The common loss of one JAK2 gene in a subgroup of melanomas suggests that this tumor might be more prone to become IFNy resistant by inactivating mutations in the second JAK2 gene. Thus, JAK2 losses could enhances the susceptibility to immunotherapy resistance.