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CD103+ Tumor-Resident CD8+ T Cells Are Associated with Improved Survival in Immunotherapy-Naïve Melanoma Patients and Expand Significantly During Anti-PD-1 Treatment.

Edwards, Jarem; Wilmott, James S; Madore, Jason; Gide, Tuba Nur; Quek, Camelia; Tasker, Annie; Ferguson, Angela; Chen, Jinbiao; Hewavisenti, Rehana; Hersey, Peter; Gebhardt, Thomas; Weninger, Wolfgang; Britton, Warwick J; Saw, Robyn P M; Thompson, John F; Menzies, Alexander M; Long, Georgina V; Scolyer, Richard A; Palendira, Umaimainthan.
Clin Cancer Res; 24(13): 3036-3045, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29599411

PURPOSE:

Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses, however, occur in less than half of those treated, and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate antitumor immune response.

PATIENTS AND METHODS:

We performed multiparameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti-PD-1 therapy.

RESULTS:

Increased numbers of CD69+CD103+ tumor-resident CD8+ T cells were associated with improved melanoma-specific survival in immunotherapy-naïve melanoma patients. Local IL15 expression levels strongly correlated with these tumor-resident T-cell numbers. The expression of several immune checkpoints including PD-1 and LAG3 was highly enriched in this subset, and these cells significantly expanded early during anti-PD-1 immunotherapy.

CONCLUSIONS:

Tumor-resident CD8+ T-cell numbers are more prognostic than total CD8+ T cells in metastatic melanoma. In addition, they are likely to initiate response to anti-PD-1 and anti-LAG-3 treatments. We propose that the immune profile of these cells prior to treatment could inform strategies for immune checkpoint blockade. Clin Cancer Res; 24(13); 3036-45. ©2018 AACR.
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