Clinically relevant T cell expansion media activate distinct metabolic programs uncoupled from cellular function

MacPherson, Sarah; Keyes, Sarah; Kilgour, Marisa K.; Smazynski, Julian; Chan, Vanessa; Sudderth, Jessica; Turcotte, Tim; Devlieger, Adria; Yu, Jessie Z.; Huggler, Kimberly S.; Cantor, Jason R.; DeBerardinis, Ralph J.; Siatskas, Christopher; Lum, Julian J.

doi:10.1016/j.omtm.2022.02.004

Cited by 24 publications

(25 citation statements)

References 55 publications

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“…Our data highlight the ability of the TCA cycle to integrate multiple fuels to support bioenergetics, biosynthesis, and effector function in T cells. One implication is that specialized media approximating physiologic conditions, such as VIM (this study) or HPLM ( Cantor et al, 2017 ), may be useful in identifying metabolic nodes relevant to T cell metabolism and function in vivo ( MacPherson et al, 2022 ). A key observation of our study is that PCSs can directly enhance CD8 + T cell effector responses.…”

Section: Discussionmentioning

confidence: 99%

Carbon source availability drives nutrient utilization in CD8+ T cells

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Carbon source availability drives nutrient utilization in CD8+ T cells

et al. 2022

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“…Thus, definitive diagnosis relies on biopsy and histopathologic analysis. In cases where suspicion for T-cell involvement is high, Roswell Park Memorial Institute (RPMI 1640) medium supplemented with 10% fetal bovine serum is most commonly used to preserve the cytoarchitecture of T-cells and promote cellular incubation and expansion after obtaining tissue biopsies [14]. Fortunately, in our case, the diagnosis could still be made despite biopsies only being preserved in a formalin solution.…”

Section: Discussionmentioning

confidence: 85%

Primary Gastrointestinal T-cell Lymphoma Presenting as Spontaneous Perforation Peritonitis

Love¹,

Rakhshandeh²,

Kheirkhah³

et al. 2023

Cureus

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Primary T-cell non-Hodgkin lymphoma (NHL) of the gastrointestinal tract (GIT) is a rare, poorlycharacterized clinical entity. A well-known complication of intestinal NHL is perforation due to chemotherapy, but perforation as a presenting sign of GIT lymphoma is extremely rare. Here we present a case of spontaneous intestinal perforation secondary to primary intestinal T-cell lymphoma and highlight the importance of early recognition of this uncommon cause of perforation as a crucial step to ensure expedited hematology referral and initiation of appropriate treatment.

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“…A recent study exploring the impact of several different media formulations on cell therapy products found that exposure to ascites from ovarian cancer patients reduced IFN-y and tumor necrosis factor alpha (TNF-a) production by T cells regardless of expansion condition. However, there were differences in the extent to which ascites exposure reduced viability, cytokine production, and mitochondrial activity, suggesting that different media formulations with varying levels of nutrients can affect T cell resilience in TME-like conditions ( 123 ). Additionally, supplementing with interleukin-7 and -15 in culture during T cell expansion can promote a central memory phenotype and robust antitumor function ( 124 ); IL-7 has been found to induce expression of glycerol channel aquaporin 9 (AQP9) on memory T cells, which imports glycerol for fatty acid esterification and triglyceride synthesis required for survival ( 125 ).…”

Section: Strategies For Improving Tcr-t Screening and Engineeringmentioning

confidence: 99%

Overcoming current challenges to T-cell receptor therapy via metabolic targeting to increase antitumor efficacy, durability, and tolerability

Mao

2022

Front. Immunol.

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The antitumor potential of personalized immunotherapy, including adoptive T-cell therapy, has been shown in both preclinical and clinical studies. Combining cell therapy with targeted metabolic interventions can further enhance therapeutic outcomes in terms of magnitude and durability. The ability of a T cell receptor to recognize peptides derived from tumor neoantigens allows for a robust yet specific response against cancer cells while sparing healthy tissue. However, there exist challenges to adoptive T cell therapy such as a suppressive tumor milieu, the fitness and survival of transferred cells, and tumor escape, all of which can be targeted to further enhance the antitumor potential of T cell receptor-engineered T cell (TCR-T) therapy. Here, we explore current strategies involving metabolic reprogramming of both the tumor microenvironment and the cell product, which can lead to increased T cell proliferation, survival, and anti-tumor cytotoxicity. In addition, we highlight potential metabolic pathways and targets which can be leveraged to improve engraftment of transferred cells and obviate the need for lymphodepletion, while minimizing off-target effects. Metabolic signaling is delicately balanced, and we demonstrate the need for thoughtful and precise interventions that are tailored for the unique characteristics of each tumor. Through improved understanding of the interplay between immunometabolism, tumor resistance, and T cell signaling, we can improve current treatment regimens and open the door to potential synergistic combinations.

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Clinically relevant T cell expansion media activate distinct metabolic programs uncoupled from cellular function

Cited by 24 publications

References 55 publications

Carbon source availability drives nutrient utilization in CD8+ T cells

Carbon source availability drives nutrient utilization in CD8+ T cells

Primary Gastrointestinal T-cell Lymphoma Presenting as Spontaneous Perforation Peritonitis

Overcoming current challenges to T-cell receptor therapy via metabolic targeting to increase antitumor efficacy, durability, and tolerability

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