Skip to Main content Skip to Navigation
Journal articles

Functional heterogeneity of cytotoxic T cells and tumor resistance to cytotoxic hits limit anti‐tumor activity in vivo

Abstract : Cytotoxic T cells (CTLs) can eliminate tumor cells through the delivery of lethal hits, but the actual efficiency of this process in the tumor microenvironment is unclear. Here, we visualized the capacity of single CTLs to attack tumor cells in vitro and in vivo using genetically encoded reporters that monitor cell damage and apoptosis. Using two distinct malignant B-cell lines, we found that the majority of cytotoxic hits delivered by CTLs in vitro were sublethal despite proper immunological synapse formation, and associated with reversible calcium elevation and membrane damage in the targets. Through intravital imaging in the bone marrow, we established that the majority of CTL interactions with lymphoma B cells were either unproductive or sublethal. Functional heterogeneity of CTLs contributed to diverse outcomes during CTL-tumor contacts in vivo. In the therapeutic settings of anti-CD19 CAR T cells, the majority of CAR T cell-tumor interactions were also not associated with lethal hit delivery. Thus, differences in CTL lytic potential together with tumor cell resistance to cytotoxic hits represent two important bottlenecks for antitumor responses in vivo.
Document type :
Journal articles
Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03261457
Contributor : Bérengère Hugot <>
Submitted on : Thursday, June 17, 2021 - 9:47:28 AM
Last modification on : Tuesday, July 13, 2021 - 3:15:33 AM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : 2021-10-15

Please log in to resquest access to the document

Licence


Distributed under a Creative Commons Attribution - NonCommercial 4.0 International License

Identifiers

Collections

Citation

Roxana Khazen, Marine Cazaux, Fabrice Lemaître, Beatrice Corre, Zacarias Garcia, et al.. Functional heterogeneity of cytotoxic T cells and tumor resistance to cytotoxic hits limit anti‐tumor activity in vivo. EMBO Journal, EMBO Press, 2021, 40 (11), pp.e106658. ⟨10.15252/embj.2020106658⟩. ⟨pasteur-03261457⟩

Share

Metrics

Record views

76