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
Type 2 diabetes mellitus (T2D) is a metabolic disease that is strongly tied to obesity and often preceded by insulin resistance (IR). It has been established that chronic inflammation of hypertrophic adipose tissue depots in obese individuals leads to obesity-associated IR and is mediated by cells of the innate immune system, particularly macrophages. More recently, cells of the adaptive immune system, B and T lymphocytes, have also emerged as important regulators of glucose homeostasis, raising the intriguing possibility that antigen-driven immune responses play a role in disease. In this review, we critically evaluate the roles that various B and T cell subsets play in IR, and then we examine the data suggesting that antigen-driven mechanisms, such as antigen presentation and costimulation, may drive the activity of these lymphocytes.
View details for DOI 10.1155/2015/593075
View details for Web of Science ID 000356285300001
View details for PubMedID 26146464
View details for PubMedCentralID PMC4471324