Association of TIM-3 expression with glucose metabolism in Jurkat T cells

Lee, Mi Jin; Yun, Su Jin; Lee, Bokyoung; Jeong, Eun; Yoon, Gyesoon; Kim, Kyongmin; Park, Sun

doi:10.1186/s12865-020-00377-6

Cited by 32 publications

(15 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have taken this approach in part because of the aforementioned complexity in Tim-3 ligands. Based on previous studies from our group and others, we believe that such overexpression results in enhanced Tim-3 signaling ( Avery et al, 2018 ; Lee et al, 2011 , 2020 ). Indeed, our finding that Treg cells expressing endogenous levels of Tim-3 display a very similar phenotype to the Tim-3 Tg Treg cells supports this assertion.…”

Section: Discussionmentioning

confidence: 80%

Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

et al. 2021

View full text Add to dashboard Cite

SUMMARY Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3 + Treg cells may be a relevant therapeutic target cell type for the treatment of cancer.

show abstract

Section: Discussionmentioning

confidence: 80%

Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

et al. 2021

View full text Add to dashboard Cite

show abstract

“…PD1, TIGIT and TIM3 checkpoint inhibitory receptors can affect the glycolytic metabolism (28)(29)(30), but our results suggested that specific combinations of these receptors might differentially affect glycolysis induction and function of CD8+ T cells from ST-ARTp and LT-ARTp. Supporting this possibility, we observed significant positive correlations between the increase on glycolytic capacities, defined by delta ECAR from basal versus maximum values after TCR activation on CD8+ T cell, and the percentages of single positive TIGIT or TIM3 expression from the total CM or EM cells (Figure 5A-B, upper panels; Supplementary figure 8B-C, upper panels).…”

Section: Combined Blockade Of Checkpoint Inhibitory Receptors and Adm...mentioning

confidence: 58%

“…It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted January 16, 2022. ; https://doi.org/10.1101/2022.01.14.476403 doi: bioRxiv preprint process involving expression of multiple checkpoint inhibitory receptors that drive the transition, survival and function of distinct memory cell subsets (24,26,27). Importantly, expression of checkpoint inhibitory receptors such as PD1, TIGIT and TIM3 in T cells is also associated with deregulated glucose metabolism (28)(29)(30), which could lead to impaired effector function and longevity of HIV-1 specific CD8+ T cells (31)(32)(33). In fact, compromise of metabolic fitness has been reported in PLWH and suggested to affect CD8+ T cell function (34,35).…”

Section: Introductionmentioning

confidence: 99%

ART duration and immunometabolic state determine efficacy of DC-based treatment restoring functional HIV- specific CD8+ T cells in PLWH

Calvet‐Mirabent

Sánchez‐Cerrillo

Martín-Cófreces

et al. 2022

Preprint

View full text Add to dashboard Cite

Dysfunction of CD8+ T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8+ T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8+ T cells after DC treatment have not been investigated in detail. Here, we studied the association of ART duration with memory subsets, exhaustion and metabolic profiles of CD8+ T cells from PLWH and improvement of polyfunctional and effector HIV-1 specific responses after stimulation with Gag-adjuvant-primed DC. HIV-1-specific CD8+ T cell responses from a larger proportion PLWH on ART for more than 10 years (LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24+ infected CD4+ T cells in vitro. In contrast, CD8+ T cells from PLWH on ART for less than a decade (ST-ARTp) were less responsive to DC treatment and functional improvement was limited in this group. This was associated with lower frequencies of central memory CD8+ T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolytic induction upon TCR activation. In contrast, CD8+ T cells from LT-ARTp showed increased frequencies of TIM3+PD1- cells and preserved induction of glycolysis. Treatment of dysfunctional CD8+ T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4+ T cells. Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines.

show abstract

“…Similarly, CTLA-4 engagement on T cell surface dampens the activation of PI3K/Akt/mTOR [ 105 ], and therefore reduces glycolysis. Knock-out of TIM-3 in an in vitro T cell model reduces glucose uptake and glycolysis [ 106 ]. Overall, given the connections mentioned above between metabolism and migration in T cells, the effects of these inhibitory co-receptors on T-cell motility described above may also depend on the concomitant alteration of T-cell metabolism.…”

Section: Metabolism and T-cell Migration Within Tumorsmentioning

confidence: 99%

Immune Checkpoint Proteins, Metabolism and Adhesion Molecules: Overlooked Determinants of CAR T-Cell Migration?

Simula

Ollivier

Icard

et al. 2022

Cells

View full text Add to dashboard Cite

Adoptive transfer of T cells genetically engineered to express chimeric antigen receptors (CAR) has demonstrated striking efficacy for the treatment of several hematological malignancies, including B-cell lymphoma, leukemia, and multiple myeloma. However, many patients still do not respond to this therapy or eventually relapse after an initial remission. In most solid tumors for which CAR T-cell therapy has been tested, efficacy has been very limited. In this context, it is of paramount importance to understand the mechanisms of tumor resistance to CAR T cells. Possible factors contributing to such resistance have been identified, including inherent CAR T-cell dysfunction, the presence of an immunosuppressive tumor microenvironment, and tumor-intrinsic factors. To control tumor growth, CAR T cells have to migrate actively enabling a productive conjugate with their targets. To date, many cells and factors contained within the tumor microenvironment have been reported to negatively control the migration of T cells and their ability to reach cancer cells. Recent evidence suggests that additional determinants, such as immune checkpoint proteins, cellular metabolism, and adhesion molecules, may modulate the motility of CAR T cells in tumors. Here, we review the potential impact of these determinants on CAR T-cell motility, and we discuss possible strategies to restore intratumoral T-cell migration with a special emphasis on approaches targeting these determinants.

show abstract

Association of TIM-3 expression with glucose metabolism in Jurkat T cells

Cited by 32 publications

References 43 publications

Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

ART duration and immunometabolic state determine efficacy of DC-based treatment restoring functional HIV- specific CD8+ T cells in PLWH

Immune Checkpoint Proteins, Metabolism and Adhesion Molecules: Overlooked Determinants of CAR T-Cell Migration?

Contact Info

Product

Resources

About