Dataset Information


PD-1+ Polyfunctional T Cells Dominate the Periphery after Tumor-Infiltrating Lymphocyte Therapy for Cancer.

ABSTRACT: Purpose: Infusion of highly heterogeneous populations of autologous tumor-infiltrating lymphocytes (TIL) can result in tumor regression of exceptional duration. Initial tumor regression has been associated with persistence of tumor-specific TILs 1 month after infusion, but mechanisms leading to long-lived memory responses are currently unknown. Here, we studied the dynamics of bulk tumor-reactive CD8+ T-cell populations in patients with metastatic melanoma following treatment with TILs.Experimental Design: We analyzed the function and phenotype of tumor-reactive CD8+ T cells contained in serial blood samples of 16 patients treated with TILs.Results: Polyfunctional tumor-reactive CD8+ T cells accumulated over time in the peripheral lymphocyte pool. Combinatorial analysis of multiple surface markers (CD57, CD27, CD45RO, PD-1, and LAG-3) showed a unique differentiation pattern of polyfunctional tumor-reactive CD8+ T cells, with highly specific PD-1 upregulation early after infusion. The differentiation and functional status appeared largely stable for up to 1 year after infusion. Despite some degree of clonal diversification occurring in vivo within the bulk tumor-reactive CD8+ T cells, further analyses showed that CD8+ T cells specific for defined tumor antigens had similar differentiation status.Conclusions: We demonstrated that tumor-reactive CD8+ T-cell subsets that persist after TIL therapy are mostly polyfunctional, display a stable partially differentiated phenotype, and express high levels of PD-1. These partially differentiated PD-1+ polyfunctional TILs have a high capacity for persistence and may be susceptible to PD-L1/PD-L2-mediated inhibition. Clin Cancer Res; 23(19); 5779-88. ©2017 AACR.


PROVIDER: S-EPMC7115919 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC5955104 | BioStudies
1000-01-01 | S-EPMC5342092 | BioStudies
1000-01-01 | S-EPMC4001555 | BioStudies
2018-01-01 | S-EPMC5884516 | BioStudies
2020-01-01 | S-EPMC7549459 | BioStudies
1000-01-01 | S-EPMC5353900 | BioStudies
2020-01-01 | S-EPMC7416171 | BioStudies
2013-01-01 | S-EPMC3748336 | BioStudies
2020-01-01 | S-EPMC7054305 | BioStudies
2014-01-01 | S-EPMC3947326 | BioStudies