Circulating Tumor Cells Shielded with Extracellular Vesicle-derived CD45 Evade T Cell Attack to Enable Metastasis

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2024 Apr 4

PMID 38575583

Authors

Chuan Yang

Xueping Wang

Kenneth K W To

Caimei Cui

Min Luo

Shaocong Wu

Lamei Huang

Kai Fu

Can Pan

Zeyu Liu

Teng Fan

Caibo Yang

Fang Wang

Liwu Fu

Affiliations

Soon will be listed here.

Abstract

Circulating tumor cells (CTCs) are precursors of distant metastasis in a subset of cancer patients. A better understanding of CTCs heterogeneity and how these CTCs survive during hematogenous dissemination could lay the foundation for therapeutic prevention of cancer metastasis. It remains elusive how CTCs evade immune surveillance and elimination by immune cells. In this study, we unequivocally identified a subpopulation of CTCs shielded with extracellular vesicle (EVs)-derived CD45 (termed as CD45 CTCs) that resisted T cell attack. A higher percentage of CD45 CTCs was found to be closely correlated with higher incidence of metastasis and worse prognosis in cancer patients. Moreover, CD45 tumor cells orchestrated an immunosuppressive milieu and CD45 CTCs exhibited remarkably stronger metastatic potential than CD45 CTCs in vivo. Mechanistically, CD45 expressing on tumor surfaces was shown to form intercellular CD45-CD45 homophilic interactions with CD45 on T cells, thereby preventing CD45 exclusion from TCR-pMHC synapse and leading to diminished TCR signaling transduction and suppressed immune response. Together, these results pointed to an underappreciated capability of EVs-derived CD45-dressed CTCs in immune evasion and metastasis, providing a rationale for targeting EVs-derived CD45 internalization by CTCs to prevent cancer metastasis.

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