English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

as a powerful therapeutic intervention against various malignancies. In past few years remarkable clinical successes have been achieved in treating cancer patient’s by bolstering the anti-tumor T cell response either by adoptively transferring tumor epitope specific TCR or CAR engineered T cells or by antibody mediated blockade of co-inhibitory immune checkpoints (PD1, CTLA4, Lag3, Tim3) on tumor reactive T cells [1]. While these therapies benefit a fraction of patients with malignancy, majority of them either do not respond to these therapies or experience tumor relapse after initial response due to T cell dysfunction in the tumor microenvironment. Therefore, understanding the T cell intrinsic factors that would instill tumor reactive T cells with a stable functional state at the tumor site is warranted. Recent studies have demonstrated that the T cell dysfunctionality in tumors is a dynamic process, which involves remodeling of the epigenetic pathways that lead to a compact chromatin state and reduced transcription of genes associated with effector function [2]. Additionally, the cellular energetic pathway is also a key feature of the unresponsive state of anti-tumor T cells. Most intriguingly, mitochondrial quality and integrity that ensures efficient oxidative phosphorylation (OXPHOS) appears to be decisive in regulating the durability and ability of the anti-tumor T cells to respond to immunotherapeutic regimen [3]. However, what connects these seemingly unrelated cellular events of attaining a distinct chromatin and metabolic state that reinforces the stable dysfunction in anti-tumor T cells. Recently, using tumor epitope reactive T cells that were ex vivo programmed to secrete both IFN-γ and IL17 at the time of adoptive transfer, we identified that CD38NAD+-Sirt1 axis acts as a key determinant of the therapeutic efficacy of anti-tumor T cells [4] (Figure 1). CD38 is an ectonucleotidase with NADase activity highly expressed on tumor infiltrating lymphocytes (TILs), and its expression increases as tumor progresses. T cells with genetic ablation of CD38 not only exhibited complete remission of tumor growth but also improved the durability of the response. Most, notable feature observed in T cells with CD38 deficiency was its preferential reliance on glutaminolysis to empower OXPHOS. We believe that thid metabolic reprogramming is critical to sustain the effector Editorial

CD38-NAD+-Sirt1 axis in T cell immunotherapy