Microenvironmental immune cell signatures dictate clinical outcomes for PTCL-NOS

Takeshi Sugio, Kohta Miyawaki, Koji Kato, Kensuke Sasaki, Kyohei Yamada, Javeed Iqbal, Toshihiro Miyamoto, Koichi Ohshima, Takahiro Maeda, Hiroaki Miyoshi, Koichi Akashi

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5 Scopus citations

Abstract

Peripheral T-cell lymphoma (PTCL), not otherwise specified (PTCL-NOS) is among the most common disease subtypes of PTCL, one that exhibits heterogeneous clinicopathological features. Although multiple disease-stratification models, including the cell-of-origin or gene-expression profiling methods, have been proposed for this condition, their clinical significance remains unclear. To establish a clinically meaningful stratification model, we analyzed gene-expression signatures of tumors and tumor-infiltrating immune cells using the nCounter system, which enables accurate quantification of low abundance and/or highly fragmented transcripts. To do so, we assessed transcripts of 120 genes related to cancer or immune cells using tumor samples from 68 newly diagnosed PTCL-NOS patients and validated findings by immunofluorescence in tumor sections. We show that gene-expression signatures representing tumor-infiltrating immune cells, but not those of cancerous T cells, dictate patient clinical outcomes. Cases exhibiting both B-cell and dendritic cell (DC) signatures (BD subgroup) showed favorable clinical outcomes, whereas those exhibiting neither B-cell nor DC signatures (non-BD subgroup) showed extremely poor prognosis. Notably, half of the non-BD cases exhibited a macrophage signature, and macrophage infiltration was evident in those cases, as revealed by immunofluorescence. Importantly, tumor-infiltrating macrophages expressed the immune-checkpoint molecules programmed death ligand 1/2 and indoleamine 2, 3-dioxygenase 1 at high levels, suggesting that checkpoint inhibitors could serve as therapeutic options for patients in this subgroup. Our study identifies clinically distinct subgroups of PTCL-NOS and suggests a novel therapeutic strategy for 1 subgroup associated with a poor prognosis. Our data also suggest functional interactions between cancerous T cells and tumor-infiltrating immune cells potentially relevant to PTCL-NOS pathogenesis.

Original languageEnglish (US)
Pages (from-to)2242-2252
Number of pages11
JournalBlood Advances
Volume2
Issue number17
DOIs
Publication statusPublished - Sep 11 2018

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ASJC Scopus subject areas

  • Hematology

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Sugio, T., Miyawaki, K., Kato, K., Sasaki, K., Yamada, K., Iqbal, J., ... Akashi, K. (2018). Microenvironmental immune cell signatures dictate clinical outcomes for PTCL-NOS. Blood Advances, 2(17), 2242-2252. https://doi.org/10.1182/pbloodadvances.2018018754