Edgar Engleman, Doctoral Dissertation Advisor (AC)
Cutting Edge: Engineering Active IKKß in T Cells Drives Tumor Rejection.
Journal of immunology
2016; 196 (7): 2933-2938
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-κB activity, which is required for tumor rejection. Impaired T cell-intrinsic NF-κB may create a vicious cycle conducive to tumor progression and further T cell dysfunction. We hypothesized that forcing T cell-intrinsic NF-κB activation might break this cycle and induce tumor elimination. NF-κB was activated in T cells by inducing the expression of a constitutively active form of the upstream activator IκB kinase β (IKKβ). T cell-restricted constitutively active IKKβ augmented the frequency of functional tumor-specific CD8(+) T cells and improved tumor control. Transfer of constitutively active IKKβ-transduced T cells also boosted endogenous T cell responses that controlled pre-established tumors. Our results demonstrate that driving T cell-intrinsic NF-κB can result in tumor control, thus identifying a pathway with potential clinical applicability.
View details for DOI 10.4049/jimmunol.1501144
View details for PubMedID 26903482
View details for PubMedCentralID PMC4799771
T cell-NF-κB activation is required for tumor control in vivo
Journal for Immunotherapy of Cancer
2015; 3 (1)
View details for DOI 10.1186/s40425-014-0045-x
- Adaptive Immunity and Antigen-Specific Activation in Obesity-Associated Insulin Resistance MEDIATORS OF INFLAMMATION 2015