AI Article Synopsis

  • Tumors can evade the immune system by causing dysfunction in tumor-reactive T cells, diminishing their ability to reject tumors.
  • Activating NF-κB within T cells may disrupt this dysfunction cycle and encourage tumor elimination.
  • The study shows that enhancing NF-κB in T cells through a specific genetic modification increases the number of effective tumor-fighting T cells and improves the immune response against existing tumors.

Article 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-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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4799771PMC
http://dx.doi.org/10.4049/jimmunol.1501144DOI Listing

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