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Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells.


ABSTRACT: An improved understanding of the anti-tumor CD8+ T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8+ tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8+ TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1- TILs. These cells could be divided into subsets bearing characterstics of naive-, effector-, and memory-precursor-like cells. Effector- and memory-precursor-like TILs contained tumor-antigen-specific cells, exhibited proliferative and effector capacity, and expanded in response to different checkpoint blockade therapies across different tumor models. The memory-precursor-like subset shared features with CD8+ T cells associated with response to checkpoint blockade in patients and was compromised in the absence of Tcf7. Expression of Tcf7/Tcf1 was requisite for the efficacy of diverse immunotherapies, highlighting the importance of this transcriptional regulator in the development of effective CD8+ T cell responses upon immunotherapy.

SUBMITTER: Kurtulus S 

PROVIDER: S-EPMC6336113 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1<sup>-</sup>CD8<sup>+</sup> Tumor-Infiltrating T Cells.

Kurtulus Sema S   Madi Asaf A   Escobar Giulia G   Klapholz Max M   Nyman Jackson J   Christian Elena E   Pawlak Mathias M   Dionne Danielle D   Xia Junrong J   Rozenblatt-Rosen Orit O   Kuchroo Vijay K VK   Regev Aviv A   Anderson Ana C AC  

Immunity 20190108 1


An improved understanding of the anti-tumor CD8<sup>+</sup> T cell response after checkpoint blockade would enable more informed and effective therapeutic strategies. Here we examined the dynamics of the effector response of CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) after checkpoint blockade therapy. Bulk and single-cell RNA profiles of CD8<sup>+</sup> TILs after combined Tim-3+PD-1 blockade in preclinical models revealed significant changes in the transcriptional profile of PD-1<sup  ...[more]

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