A Population of Tumor-Infiltrating CD4+ T Cells Co-Expressing CD38 and CD39 Is Associated with Checkpoint Inhibitor Resistance.
Clin Cancer Res
; 29(20): 4242-4255, 2023 10 13.
Article
en En
| MEDLINE
| ID: mdl-37505479
ABSTRACT
PURPOSE:
We previously showed that elevated frequencies of peripheral blood CD3+CD4+CD127-GARP-CD38+CD39+ 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 (Teee). EXPERIMENTALDESIGN:
Teee derived from the peripheral blood of patients with metastatic melanoma were evaluated by bulk RNA-sequencing (RNA-seq) and flow cytometry. The presence of Teee 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 Teee was determined by an in vitro autologous suppression assay.RESULTS:
Teee had phenotypes associated with proliferation, apoptosis, exhaustion, and high expression of inhibitory molecules. Cells with a Teee gene signature were present in tumors of patients with melanoma, lung, and bladder cancers. CD4+ T cells co-expressing CD38 and CD39 in the tumor microenvironment were preferentially associated with Ki67- CD8+ T cells. Co-culture of patient Teee with autologous T cells resulted in decreased proliferation of target T cells. High baseline intratumoral frequencies of Teee were associated with checkpoint immunotherapy resistance and poor overall survival in patients with metastatic melanoma.CONCLUSIONS:
These results demonstrate that a novel population of CD4+ 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Vejiga Urinaria
/
Melanoma
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article