Title

Tumor cell-released autophagosomes (TRAP) enhance apoptosis and immunosuppressive functions of neutrophils.

Document Type

Article

Publication Date

1-1-2018

Keywords

apoptosis; T cell; macropinocytosis; immune evasion; neutrophil; reactive oxygen species(ROS); tumor cel-lreleased autophagosomes (TRAP)

Abstract

Our previous studies have confirmed that tumor cell-released autophagosomes (TRAP) could induce the differentiation of B cells into IL-10+regulatory B cells (Bregs) with suppressive activities on T lymphocytes. However, the mechanism of TRAP-mediated immune suppression is still largely unclear. Herein, we sought to assess the immunomodulatory effect of TRAPs on human neutrophils, a major immune cell type that infiltrates human tumor tissues. We found that TRAPs enriched from malignant effusions or ascites of cancer patients and tumor cell lines were rapidly and effectively phagocytized by neutrophils through macropinocytosis and promoted neutrophil apoptosis via reactive oxygen species (ROS) generation and caspase-3 activation. Moreover, the apoptotic neutrophils that have phagocytized TRAPs inhibited the proliferation and activation of CD4+ T and CD8+ T cells in a cell contact- and ROS-dependent manner. These findings define a novel TRAP-mediated mechanism in neutrophils that potentially suppresses the anti-tumor T cell immunity and highlight TRAPs as an important target for future tumor immunotherapy.

Clinical Institute

Cancer

Department

Oncology

Volume

7

Issue

6

First Page

1438108

Last Page

1438108

PubMed ID

29872581

Journal Title

Oncoimmunology

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