The complex integration of T-cell metabolism and immunotherapy

MZ Madden, JC Rathmell - Cancer Discovery, 2021 - AACR
Cancer Discovery, 2021AACR
Immune oncology approaches of adoptive cell therapy and immune checkpoint blockade
aim to activate T cells to eliminate tumors. Normal stimulation of resting T cells induces
metabolic reprogramming from catabolic and oxidative metabolism to aerobic glycolysis in
effector T cells, and back to oxidative metabolism in long-lived memory cells. These
metabolic reprogramming events are now appreciated to be essential aspects of T-cell
function and fate. Here, we review these transitions, how they are disrupted by T-cell …
Abstract
Immune oncology approaches of adoptive cell therapy and immune checkpoint blockade aim to activate T cells to eliminate tumors. Normal stimulation of resting T cells induces metabolic reprogramming from catabolic and oxidative metabolism to aerobic glycolysis in effector T cells, and back to oxidative metabolism in long-lived memory cells. These metabolic reprogramming events are now appreciated to be essential aspects of T-cell function and fate. Here, we review these transitions, how they are disrupted by T-cell interactions with tumors and the tumor microenvironment, and how they can inform immune oncology to enhance T-cell function against tumors.
Significance
T-cell metabolism plays a central role in T-cell fate yet is altered in cancer in ways that can suppress antitumor immunity. Here, we discuss challenges and opportunities to stimulate effector T-cell metabolism and improve cancer immunotherapy.
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