Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+ TAM expansion

Oncogenesis
Bin LiTao Jing

Abstract

Macrophages constitute one of the most common components of immune cells, which penetrate tumors and they have a key role in tumor prognosis. Here, we identified an unrecognized macrophage subpopulation, which favors tumorigenesis. These macrophages express programmed cell death protein 1 (PD1) in a constitutive manner and accumulates in esophageal squamous cell carcinoma (ESCC) in advanced stage of the disease and is negatively associated with the survival of ESCC patients. The PD1+ tumor-associated macrophages (PD1+ TAMs) displayed surface pattern and function akin to M2: a substantial enhancement in CD206 and IL-10 expression; a specific reduction in HLA-DR, CD64, and IL-12 expression; and a significant increase in the ability to inhibit CD8+ T-cell proliferation. Triggering of PD1 signal is effective in increasing PD1+ TAM function. Moreover, exosomal HMGB1 obtained from tumors are efficient in triggering differentiation of monocytes into PD1+ TAMs, which display phenotypic and functional properties of M2. Overall, our work is the first finding to confirm that exosomal HMGB1 obtained from ESCC can successfully trigger clonal expansion of PD1+ TAM. Further, as the macrophages exhibit an M2-like surface profile and function, ...Continue Reading

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Citations

Nov 20, 2019·Medicinal Research Reviews·Tuhina KhanGiuseppe Campiani
Aug 30, 2019·Nature Reviews. Cancer·Mingye FengIrving L Weissman
Aug 9, 2020·Cancer Management and Research·Peng HanFan Li
Feb 17, 2021·Signal Transduction and Targeted Therapy·He-Ming ZhouQin Li
Nov 12, 2020·Biology·Kyra E de GoedeJan Van den Bossche
Mar 24, 2021·The Journal of Biological Chemistry·Giovanna MangiapaneGianluca Tell
Jul 3, 2021·International Journal of Molecular Sciences·Huogang WangDavid W Chan
Sep 16, 2019·International Immunopharmacology·Laleh SharifiMonireh Mohsenzadegan
Jun 22, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Weihua GuoHong Shen
Dec 7, 2021·Frontiers in Pharmacology·Lu LiShiying Yu

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Methods Mentioned

BETA
flow cytometry
ELISA
density-gradient centrifugation

Software Mentioned

flow jo
sight
Nano
FACScan

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