TY - JOUR
T1 - Is the tumor cell side of the immunological synapse a polarized secretory domain?
AU - Biolato, Andrea Michela
AU - Filali, Liza
AU - Pereira Fernandes, Diogo
AU - Moreau, Flora
AU - Mgrditchian, Takouhie
AU - Hoffmann, Céline
AU - Thomas, Clément
N1 - Grants and funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. CT’s group is supported by the Luxembourg National Research Fund (FNR, Luxembourg; C21/BM/15752542), La Fondation Cancer (Luxembourg; FC/2019/02) and Luxembourg's Ministry of Higher Education and Research (MESR). AB and DPF are recipients of PhD fellowships from Fonds De La Recherche Scientifique (FNRS, Belgium; Télévie grants 7.4536.19 and 7.4594.23, respectively). TM is recipient of a Postdoctoral fellowship from Fonds De La Recherche Scientifique (FNRS, Belgium; Télévie grant 7.4537.19). For the purpose of open access, and in fulfilment of the obligations arising from the grant agreement, the author has applied a Creative Commons Attribution 4.0 International (CC BY 4.0) license to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
Copyright © 2024 Biolato, Filali, Pereira Fernandes, Moreau, Mgrditchian, Hoffmann and Thomas.
Copyright © 2024 Biolato, Filali, Pereira Fernandes, Moreau, Mgrditchian, Hoffmann and Thomas.
PY - 2024/9/24
Y1 - 2024/9/24
N2 - The formation of a lytic immunological synapse (IS) is crucial for cytotoxic lymphocytes to accurately target and effectively eliminate malignant cells. While significant attention has been focused on the lymphocyte side of the IS, particularly its role as a secretory domain for lytic granules, the cancer cell side of the IS has remained relatively underexplored. Recent findings have revealed that cancer cells can rapidly polarize their actin cytoskeleton toward the IS upon interaction with natural killer (NK) cells, thereby evading NK cell-mediated cytotoxicity. In this Brief Research Report, we present preliminary findings suggesting that actin cytoskeleton remodeling at the cancer cell side of the IS is associated with the targeted secretion of small extracellular vesicles towards the interacting NK cell. We observed that multivesicular bodies (MVBs) preferentially accumulate in the synaptic region in cancer cells exhibiting synaptic accumulation of F-actin, compared to those lacking actin cytoskeleton remodeling. Extracellular immunofluorescence staining revealed increased surface exposure of CD63 at the cancer cell side of the IS, suggestive of the fusion of MVBs with the plasma membrane. This hypothesis was supported by a pH-sensitive probe demonstrating dynamic trafficking of CD63 to the extracellular region of the IS. Collectively, our data support the notion that cancer cells can engage in targeted secretion of extracellular vesicles in response to NK cell attack, underscoring the need for further research into the potential role of this process in facilitating cancer cell immune evasion.
AB - The formation of a lytic immunological synapse (IS) is crucial for cytotoxic lymphocytes to accurately target and effectively eliminate malignant cells. While significant attention has been focused on the lymphocyte side of the IS, particularly its role as a secretory domain for lytic granules, the cancer cell side of the IS has remained relatively underexplored. Recent findings have revealed that cancer cells can rapidly polarize their actin cytoskeleton toward the IS upon interaction with natural killer (NK) cells, thereby evading NK cell-mediated cytotoxicity. In this Brief Research Report, we present preliminary findings suggesting that actin cytoskeleton remodeling at the cancer cell side of the IS is associated with the targeted secretion of small extracellular vesicles towards the interacting NK cell. We observed that multivesicular bodies (MVBs) preferentially accumulate in the synaptic region in cancer cells exhibiting synaptic accumulation of F-actin, compared to those lacking actin cytoskeleton remodeling. Extracellular immunofluorescence staining revealed increased surface exposure of CD63 at the cancer cell side of the IS, suggestive of the fusion of MVBs with the plasma membrane. This hypothesis was supported by a pH-sensitive probe demonstrating dynamic trafficking of CD63 to the extracellular region of the IS. Collectively, our data support the notion that cancer cells can engage in targeted secretion of extracellular vesicles in response to NK cell attack, underscoring the need for further research into the potential role of this process in facilitating cancer cell immune evasion.
KW - actin cytoskeleton
KW - cancer
KW - immunological synapse
KW - multivesicular bodies (MVB)
KW - natural killer (Nk) cell
KW - targeted secretion
KW - Killer Cells, Natural/immunology
KW - Actin Cytoskeleton/metabolism
KW - Immunological Synapses/metabolism
KW - Actins/metabolism
KW - Humans
KW - Extracellular Vesicles/immunology
KW - Multivesicular Bodies/metabolism
KW - Cell Line, Tumor
KW - Neoplasms/immunology
KW - Tetraspanin 30/metabolism
KW - Cytotoxicity, Immunologic
UR - http://www.scopus.com/inward/record.url?scp=85206022345&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/39380986/
U2 - 10.3389/fimmu.2024.1452810
DO - 10.3389/fimmu.2024.1452810
M3 - Article
C2 - 39380986
AN - SCOPUS:85206022345
SN - 1664-3224
VL - 15
SP - 1452810
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1452810
ER -