Dataset Information

PET-based radiomics visualizes tumor-infiltrating CD8 T cell exhaustion to optimize radiotherapy/immunotherapy combination in mouse models of lung cancer.

ABSTRACT:

Background

Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8⁺ T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during peri-irradiation period, while dynamic monitoring is unavailable via repeated biopsies in clinical practice.

Methods

Basing on tumor-bearing mice model, we investigated the dynamics of overall infiltration and exhausted subpopulations of CD8⁺ T cells after ablative irradiation. With the understanding of distinct metabolic characteristics accompanied with T cell exhaustion, we developed a PET radiomics approach to identify and visualize T cell exhaustion status.

Results

CD8⁺ T cell infiltration increased from 3 to 14 days after ablative irradiation while terminally exhausted populations significantly predominated CD8⁺ T cells during late course of this infiltrating period, indicating that 3-7 days post-irradiation might be a potential appropriate window for delivering ICI treatment. A PET radiomics approach was established to differentiate T cell exhaustion status, which fitted well in both ICI and irradiation settings. We also visualized the underlying association of more heterogeneous texture on PET images with progressed T cell exhaustion.

Conclusions

We proposed a non-invasive imaging predictor which accurately assessed heterogeneous T cell exhaustion status relevant to ICI treatment and irradiation, and might serve as a promising solution to timely estimate immune-responsiveness of tumor microenvironment and the optimal timing of combined therapy.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9875413 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

PET-based radiomics visualizes tumor-infiltrating CD8 T cell exhaustion to optimize radiotherapy/immunotherapy combination in mouse models of lung cancer.

Zhang Ying Y Hu Hui-Hui HH Zhou Shi-Hong SH Xia Wu-Yan WY Zhang Yan Y Zhang Jian-Ping JP Fu Xiao-Long XL Yu Wen W

Biomarker research 20230125 1

<h4>Background</h4>Cumulative preclinical and clinical evidences showed radiotherapy might augment systemic antitumoral responses to immunotherapy for metastatic non-small cell lung cancer, but the optimal timing of combination is still unclear. The overall infiltration and exhausted subpopulations of tumor-infiltrating CD8<sup>+</sup> T cells might be a potential biomarker indicating the response to immune checkpoint inhibitors (ICI), the alteration of which is previously uncharacterized during ...[more]

PMID: 36694213

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Dataset Information

PET-based radiomics visualizes tumor-infiltrating CD8 T cell exhaustion to optimize radiotherapy/immunotherapy combination in mouse models of lung cancer.

Background

Methods

Results

Conclusions

Publications

PET-based radiomics visualizes tumor-infiltrating CD8 T cell exhaustion to optimize radiotherapy/immunotherapy combination in mouse models of lung cancer.

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