Cutting Edge: Engineering Active IKK? in T Cells Drives Tumor Rejection.

ABSTRACT: Acquired dysfunction of tumor-reactive T cells is one mechanism by which tumors can evade the immune system. Identifying and correcting pathways that contribute to such dysfunction should enable novel anticancer therapy design. During cancer growth, T cells show reduced NF-?B activity, which is required for tumor rejection. Impaired T cell-intrinsic NF-?B may create a vicious cycle conducive to tumor progression and further T cell dysfunction. We hypothesized that forcing T cell-intrinsic NF-?B activation might break this cycle and induce tumor elimination. NF-?B was activated in T cells by inducing the expression of a constitutively active form of the upstream activator I?B kinase ? (IKK?). T cell-restricted constitutively active IKK? augmented the frequency of functional tumor-specific CD8(+) T cells and improved tumor control. Transfer of constitutively active IKK?-transduced T cells also boosted endogenous T cell responses that controlled pre-established tumors. Our results demonstrate that driving T cell-intrinsic NF-?B can result in tumor control, thus identifying a pathway with potential clinical applicability.

SUBMITTER: Evaristo C 

PROVIDER: S-EPMC4799771 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature