Rapid communicationHuman Colorectal Cancer Cells Induce T-Cell Death Through Release of Proapoptotic Microvesicles: Role in Immune Escape
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Colorectal Cancer Lines, Colorectal Cancer Patients, and Purification of Released Microvesicles
The CRC line SW403 was purchased from the American Type Culture Collection (Manassas, VA), and 1869 col (provided by Dr C. Maccalli, Istituto Superiore di Sanità, Rome, Italy) 17 and CRC28462 were short-term lines generated from liver metastases of CRC patients. All the lines stained positively for pan-epithelial (BerEP4), cytokeratin (CD18, LP34, and MNF116), and class I HLA markers and were negative for the fibroblast marker 5B5. These lines formed colonies in soft agar, were tumorigenic in
Expression of FasL and TRAIL in Human Colorectal Cancer Cells and Their Released Microvesicles
Expression of both FasL (Figure 1A) and TRAIL (Figure 1B and C), as detected by immunocytochemistry on CRC cell lines, displayed a granular distribution that was apparently confined to the intracellular compartments. TRAIL staining seemed to vectorially accumulate either at the cell-to-cell contact sites or at the center of pseudocrypts formed in culture (Figure 1C). IEM showed FasL and TRAIL localization in defined intracellular MVs (approximately 50–100 nm), primarily located in proximity to (
Discussion
Here we report that human CRC cells induce apoptosis of T lymphocytes through the release of FasL- and TRAIL-bearing MVs. These lysosome-derived organelles, characterized by a 50–100-nm diameter and a high content of cytosolic and membrane proteins derived from the producing cell, are released by CRC in vitro and are found in plasma and tumor specimens from patients with advanced CRC. These data shed new light on the role of FasL in immune evasion of CRC. The acquired expression of this
References (30)
- et al.
Intestinal epithelial cells secrete exosome-like vesicles
Gastroenterology
(2001) - et al.
Exosomesendosomal-derived vesicles shipping extracellular messages
Curr Opin Cell Biol
(2004) - et al.
Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells
Blood
(2004) - et al.
Immunology and immunotherapy of colorectal cancer
Crit Rev Oncol Hematol
(2003) - et al.
The Fas counterattackcancer as a site of immune privilege
Immunol Today
(1999) - et al.
Functional expression of tumor necrosis factor-related apoptosis-inducing ligand in human colonic adenocarcinoma cells
Lab Invest
(2002) - et al.
Identification and characterization of a new member of the TNF family that induces apoptosis
Immunity
(1995) - et al.
Malignant effusions and immunogenic tumour-derived exosomes
Lancet
(2002) - et al.
TRAIL and its receptors in the colonic epitheliuma putative role in the defense of viral infections
Gastroenterology
(2002) - et al.
Exosomefrom internal vesicle of the multivesicular body to intercellular signaling device
J Cell Sci
(2000)
“Tolerosomes” are produced by intestinal epithelial cells
Eur J Immunol
Presentation of donor major histocompatibility complex antigens by bone marrow dendritic cell-derived exosomes modulates allograft rejection
Transplantation
Escape of human solid tumors from T-cell recognitionmolecular mechanisms and significance
Adv Immunol
The Fas counterattackFas-mediated T cell killing by colon cancer cells expressing Fas ligand
J Exp Med
The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity
Nat Immunol
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Supported by grants from the Italian Association for Cancer Research (Milan) and Fondo pergli Investimenti della Ricerca di Base, Ministero dell’Instruzione, dell’Università e della Ricerca (FIRB-MIUR) RBNE017B4C (Rome).