ArticleThe EMBO journal2021
Functional heterogeneity of cytotoxic T cells and tumor resistance to cytotoxic hits limit anti-tumor activity in vivo.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Decoupling T cell cytotoxicity: a CCL21+ICAM1-based synthetic immune niche enhances tumor elimination by accelerating lytic hit delivery.BMC cancer · 2026Article
- Imaging-guided optimization of biodistribution and antitumor efficacy of L19-based immunocytokines.Translational oncology · 2026Article
- Mapping T cell dynamics to molecular profiles through behavior-guided transcriptomics.Nature protocols · 2025Review
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Metal-modulated T cell antitumor immunity and emerging metalloimmunotherapy.Cancer metastasis reviews · 2025Review
- Intravital Imaging of Immune Responses in the Cancer Microenvironment.Cancer medicine · 2025Review
- Visualizing cellular interactions: intravital imaging in tumor microenvironment.Frontiers in immunology · 2025Review
- 3D live imaging and phenotyping of CAR-T cell mediated-cytotoxicity using high-throughput Bessel oblique plane microscopy.Nature communications · 2024Article
- BEHAV3D: a 3D live imaging platform for comprehensive analysis of engineered T cell behavior and tumor response.Nature protocols · 2024Article
- Cancer-on-a-chip model shows that the adenomatous polyposis coli mutation impairs T cell engagement and killing of cancer spheroids.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multi-omics landscape of Interferon-stimulated gene OASL reveals a potential biomarker in pan-cancer: from prognosis to tumor microenvironment.Frontiers in immunology · 2024Article
- Bridging live-cell imaging and next-generation cancer treatment.Nature reviews. Cancer · 2023Review
- Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities.Frontiers in immunology · 2023Review
- Tumour immunotherapy: lessons from predator-prey theory.Nature reviews. Immunology · 2022Review
- High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing.Nature communications · 2022Article
- Ultrarapid lytic granule release from CTLs activates CaScience advances · 2022Article
- Escaping Death: How Cancer Cells and Infected Cells Resist Cell-Mediated Cytotoxicity.Frontiers in immunology · 2022Review
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 anti-tumor responses in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.