331 research outputs found
Abstract IA03: Anti-tumor T cells: You are what you eat
No full textAbstract
Activated T cells engage aerobic glycolysis and anabolic metabolism for growth, proliferation, and effector functions. In contrast, resting memory CD8 T cells depend less on high rates of glycolysis and more on fatty acid oxidation to persist, self-renew and respond to secondary infection. This talk will discuss the concept of metabolic checkpoints for immune cells in tumors, referring to the idea that the nutrients utilized by different types of T cells can affect both their energetic demands and their functionality. In particular, the metabolic state of exhausted T cells found in tumors is only recently starting to be studied. Our data in mouse models of cancer suggest that a glucose-poor, fatty acid-rich tumor microenvironment limits aerobic glycolysis, but promotes fatty acid uptake in tumor-infiltrating T cells, which suppresses tumoricidal effector functions and increases PD-1 expression. This talk will discuss recent analyses of the signaling pathways that respond to these nutrient alterations in T cells in tumors and how this may relate to new modalities of treatment in combination with checkpoint blockade.
Citation Format: Guoliang Cui, Ping-Chih Ho, Robert Amezquita, Susan M. Kaech. Anti-tumor T cells: You are what you eat. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA03.</jats:p
Immigration in science
No full textThe advance of science is dependent upon collaboration, which does not have a visa attached to it. Indeed, over 40% of all American-based Nobel Prize winners are immigrants, and data from the National Science Foundation show that 49% of postdocs and 29% of science and engineering faculty in the US are foreign-born. However, restrictive new immigration policies in the US have left many scientists deeply concerned about their future and many American-based laboratories worried about attracting the best talent. At JEM, we're celebrating immigration by sharing the experiences of immigrant and nonimmigrant scientists on our editorial board. Alexander Rudensky and Jean-Laurent Casanova give their firsthand perspective on immigrating to the US, while Jedd Wolchok, Carl Nathan, David Holtzman, Susan Kaech, Lewis Lanier, and David Tuveson reflect on how immigration has affected their laboratories
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Canonical BAF complex activity licenses effector and memory CD8+ T cell fates
No full textCD8+ T cells provide host protection against pathogens by differentiating into distinct effector and memory cell subsets. Though many of the key transcription factors that govern effector and memory differentiation have been identified, our understanding of how differentiation is transcriptionally and epigenetically regulated is incomplete. In particular how chromatin is site-specifically remodeled during their differentiation is unclear. Given its critical role in regulating chromatin and enhancer accessibility through its nucleosome remodeling activities, we investigated the role of the canonical BAF (cBAF) chromatin remodeling complex in antiviral CD8+ T cells during infection. ARID1A, a subunit of cBAF, was recruited early after activation and established de novo open chromatin regions at enhancers. Arid1a deficiency impaired the opening of thousands of activation-induced enhancers, leading to loss of TF binding, dysregulated proliferation, gene expression, and failure to undergo terminal effector differentiation. While Arid1a was dispensable for circulating memory cell formation per se, functionality and recall capacity was strongly impaired in the absence of Arid1a. Furthermore, tissue-resident memory formation was strongly impaired in Arid1a-deficient cells. Inducible deletion of Arid1a several days after priming in vivo also led to strongly diminished terminal effector differentiation, indicating that terminal fate determining events require continuous cBAF activity in order for terminal effector cells to form. Arid1b, Pbrm1 (PBAF-specific), and Brd9 (ncBAF-specific) deletions had minimal impact on effector cell differentiation. Thus, ARID1A-containing cBAF governs the enhancer landscape of activated CD8+ T cells that orchestrates TF recruitment and activity and the acquisition of specific effector and memory differentiation states
Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naïve cells
No full textReenergizing T cell anti-tumor immunity by harnessing immunometabolic checkpoints and machineries
No full textT cells patrol our bodies preventing pathogenic infections and malignant cell outgrowth. However, T cells must be properly controlled because aberrant or persistent T cell responses can damage tissues and contribute to autoimmune diseases and other chronic inflammatory diseases including metabolic syndrome. One regulatory mechanism utilized in immune cells is immunometabolic regulation, which ensures immune cells properly respond to systemic and peripheral metabolic cues. Recent work has suggested that deregulated metabolism in tumor cells creates a microenvironmental barrier for mounting effective anti-tumor immune responses. Here, we discuss how tumor cells evade immunosurveillance by modulating metabolic checkpoints in immune cells and discuss how memory T cells could provide effective anti-tumor responses by sustaining metabolic fitness and longevity
IL-7 Knocks the Socs Off Chronic Viral Infection
No full textChronic viral infections represent a major burden to human health, and modulation of the immune system is emerging as a novel approach to fighting such infections. Pellegrini et al. (2011) demonstrate that treatment with the cytokine IL-7 may reinvigorate the immune response to persistent infection by targeting immunosuppressive Socs3 proteins
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