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Tireless surveillance by exhausted T cells
Michael L. Dustin
Michael L. Dustin
Published September 15, 2021
Citation Information: J Clin Invest. 2021;131(18):e152382. https://doi.org/10.1172/JCI152382.
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Commentary

Tireless surveillance by exhausted T cells

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Abstract

T cell exhaustion is an evocative concept that results in attenuated function in the face of chronic antigen exposure and is critical to avoid immunopathology. However, tumors often exploit this dampened T cell function to escape the antitumor immune response. In this issue of the JCI, You et al. investigated a different aspect of T cell exhaustion in the setting of tumor immunity by characterizing the capacity of T cells for tireless migration. The dynamic nature of normal T cells was first made famous by intravital microscopy studies in explanted tissues. You et al. used a similar imaging strategy with reanimated human tumors, in which exhausted T cells displayed an enhanced capacity for intratumoral motility. These results suggest that exhausted T cells may be able to teach T cell engineers lessons about navigating within the tumor microenvironment.

Authors

Michael L. Dustin

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Figure 1

Cumulative damage model for the motile exhausted T cell’s muted attack.

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Cumulative damage model for the motile exhausted T cell’s muted attack.
...
(A) Newly recruited effector T cells (blue) engage targets at the interface between the tumor (yellow) and healthy surrounding tissues, leading to effective killing of superficial tumor cells (red). (B) Later in the antitumor response, exhausted T cells (light blue) become highly motile. The highly motile exhausted T cells may penetrate the tumor better, but are also weaker effectors, so they need to inflict cumulative damage through many encounters to kill tumor cells (red). The mobility program of exhausted T cells could be useful in immunotherapy applications that improve T cell numbers and/or potency to increase deep tumor killing.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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