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- W4387609610 abstract "<div>AbstractPurpose:<p>We previously showed that elevated frequencies of peripheral blood CD3<sup>+</sup>CD4<sup>+</sup>CD127<sup>−</sup>GARP<sup>−</sup>CD38<sup>+</sup>CD39<sup>+</sup> T cells were associated with checkpoint immunotherapy resistance in patients with metastatic melanoma. In the present study, we sought to further investigate this population of ectoenzyme-expressing T cells (T<sub>eee</sub>).</p>Experimental Design:<p>T<sub>eee</sub> derived from the peripheral blood of patients with metastatic melanoma were evaluated by bulk RNA-sequencing (RNA-seq) and flow cytometry. The presence of T<sub>eee</sub> in the tumor microenvironment was assessed using publically available single-cell RNA-seq datasets of melanoma, lung, and bladder cancers along with multispectral immunofluorescent imaging of melanoma patient formalin-fixed, paraffin-embedded specimens. Suppressive function of T<sub>eee</sub> was determined by an <i>in vitro</i> autologous suppression assay.</p>Results:<p>T<sub>eee</sub> had phenotypes associated with proliferation, apoptosis, exhaustion, and high expression of inhibitory molecules. Cells with a T<sub>eee</sub> gene signature were present in tumors of patients with melanoma, lung, and bladder cancers. CD4<sup>+</sup> T cells co-expressing CD38 and CD39 in the tumor microenvironment were preferentially associated with Ki67<sup>−</sup> CD8<sup>+</sup> T cells. Co-culture of patient T<sub>eee</sub> with autologous T cells resulted in decreased proliferation of target T cells. High baseline intratumoral frequencies of T<sub>eee</sub> were associated with checkpoint immunotherapy resistance and poor overall survival in patients with metastatic melanoma.</p>Conclusions:<p>These results demonstrate that a novel population of CD4<sup>+</sup> T cells co-expressing CD38 and CD39 is found both in the peripheral blood and tumor of patients with melanoma and is associated with checkpoint immunotherapy resistance.</p></div>" @default.
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- W4387609610 date "2023-10-13" @default.
- W4387609610 modified "2023-10-15" @default.
- W4387609610 title "Data from A Population of Tumor-Infiltrating CD4<sup>+</sup> T Cells Co-Expressing CD38 and CD39 Is Associated with Checkpoint Inhibitor Resistance" @default.
- W4387609610 doi "https://doi.org/10.1158/1078-0432.c.6879395.v1" @default.
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