Dynamic visualization of the whole process of cytotoxic T lymphocytes killing B16 tumor cells in vitro

Qi, Shuhong; Shi, Hua; Liu, Lei; Zhou, Lili

doi:10.1117/1.jbo.24.5.051413

Cited by 7 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further in vitro studies highlighted that killing by CTLs may kill multiple targets rapidly [ 17 , 18 , 19 ], but also highlighted heterogeneity in the efficacy at which individual CTLs kill their targets [ 20 , 21 ]. Interestingly, killing of tumor cells in vitro may take a long time (hours) with speed and turning being important in determining the likelihood that a CTL will find and kill the target [ 22 , 23 ]. One study suggested that killing of targets in vitro may follow the law of mass–action [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T Lymphocytes Control Growth of B16 Tumor Cells in Collagen–Fibrin Gels by Cytolytic and Non-Lytic Mechanisms

Majumder

Budhu

Ganusov

2023

Viruses

View full text Add to dashboard Cite

Cytotoxic T lymphocytes (CTLs) are important in controlling some viral infections, and therapies involving the transfer of large numbers of cancer-specific CTLs have been successfully used to treat several types of cancers in humans. While the molecular mechanisms of how CTLs kill their targets are relatively well understood, we still lack a solid quantitative understanding of the kinetics and efficiency by which CTLs kill their targets in vivo. Collagen–fibrin-gel-based assays provide a tissue-like environment for the migration of CTLs, making them an attractive system to study T cell cytotoxicity in in vivo-like conditions. Budhu.et al. systematically varied the number of peptide (SIINFEKL)-pulsed B16 melanoma cells and SIINFEKL-specific CTLs (OT-1) and measured the remaining targets at different times after target and CTL co-inoculation into collagen–fibrin gels. The authors proposed that their data were consistent with a simple model in which tumors grow exponentially and are killed by CTLs at a per capita rate proportional to the CTL density in the gel. By fitting several alternative mathematical models to these data, we found that this simple “exponential-growth-mass-action-killing” model did not precisely describe the data. However, determining the best-fit model proved difficult because the best-performing model was dependent on the specific dataset chosen for the analysis. When considering all data that include biologically realistic CTL concentrations (E≤107cell/mL), the model in which tumors grow exponentially and CTLs suppress tumor’s growth non-lytically and kill tumors according to the mass–action law (SiGMA model) fit the data with the best quality. A novel power analysis suggested that longer experiments (∼3–4 days) with four measurements of B16 tumor cell concentrations for a range of CTL concentrations would best allow discriminating between alternative models. Taken together, our results suggested that the interactions between tumors and CTLs in collagen–fibrin gels are more complex than a simple exponential-growth-mass–action killing model and provide support for the hypothesis that CTLs’ impact on tumors may go beyond direct cytotoxicity.

show abstract

Section: Introductionmentioning

confidence: 99%

Cytotoxic T Lymphocytes Control Growth of B16 Tumor Cells in Collagen–Fibrin Gels by Cytolytic and Non-Lytic Mechanisms

Majumder

Budhu

Ganusov

2023

Viruses

View full text Add to dashboard Cite

show abstract

“…Further in vitro studies highlighted that killing by CTLs may kill multiple targets rapidly [18][19][20] but also highlighted heterogeneity in efficacy at which individual CTLs kill their targets [21,22]. Interestingly, killing of tumor cells in vitro may take long time (hours) with speed and turning being important in determining the likelihood that a CTL will find and kill the target [23,24]. One study suggested that killing of targets in vitro may follow the law of mass-action [25].…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling suggests cytotoxic T lymphocytes control growth of B16 tumor cells in collagin-fibrin gels by cytolytic and non-lytic mechanisms

Majumder

Budhu

Ganusov

2023

Preprint

View full text Add to dashboard Cite

Cytotoxic T lymphocytes (CTLs) are important in controlling some viral infections, and therapies involving transfer of large numbers of cancer-specific CTLs have been successfully used to treat several types of cancers in humans. While molecular mechanisms of how CTLs kill their targets are relatively well understood we still lack solid quantitative understanding of the kinetics and efficiency at which CTLs kill their targets in different conditions. Collagen-fibrin gel-based assays provide a tissue-like environment for the migration of CTLs, making them an attractive system to study the cytotoxicity in vitro. Budhu et al. [1] systematically varied the number of peptide (SIINFEKL)-pulsed B16 melanoma cells and SIINFEKL-specific CTLs (OT-1) and measured remaining targets at different times after target and CTL co-inoculation into collagen-fibrin gels. The authors proposed that their data were consistent with a simple model in which tumors grow exponentially and are killed by CTLs at a per capita rate proportional to the CTL density in the gel. By fitting several alternative mathematical models to these data we found that this simple ``exponential-growth-mass-action-killing'' model does not precisely fit the data. However, determining the best fit model proved difficult because the best performing model was dependent on the specific dataset chosen for the analysis. When considering all data that include biologically realistic CTL concentrations ($E<=10^7 cell/ml) the model in which tumors grow exponentially and CTLs suppress tumor's growth non-lytically and kill tumors according to the mass-action law (SiGMA model) fitted the data with best quality. Results of power analysis suggested that longer experiments (3-4 days) with 4 measurements of B16 tumor cell concentrations for a range of CTL concentrations would best allow to discriminate between alternative models. Taken together, our results suggest that interactions between tumors and CTLs in collagen-fibrin gels are more complex than a simple exponential-growth-mass-action killing model and provide support for the hypothesis that CTLs impact on tumors may go beyond direct cytotoxicity.

show abstract

“…This research develops and/or uses optical tools to measure functional processes in healthy and diseased cells and tissues. We have classified these manuscripts into five categories: metabolism, 2,3 perfusion, 4 cancer imaging/monitoring, 5,6,7,8 functional brain monitoring, 9,10 and technology development. 11,12,13,14 Britton Chance was deeply interested in all of these subfields of biomedical optics.…”

mentioning

confidence: 99%

Special Section Guest Editorial: Celebration of the Britton Chance Legacy

Busch

Yodh

2019

J. Biomed. Opt.

View full text Add to dashboard Cite

show abstract

Dynamic visualization of the whole process of cytotoxic T lymphocytes killing B16 tumor cells in vitro

Cited by 7 publications

References 40 publications

Cytotoxic T Lymphocytes Control Growth of B16 Tumor Cells in Collagen–Fibrin Gels by Cytolytic and Non-Lytic Mechanisms

Cytotoxic T Lymphocytes Control Growth of B16 Tumor Cells in Collagen–Fibrin Gels by Cytolytic and Non-Lytic Mechanisms

Mathematical modeling suggests cytotoxic T lymphocytes control growth of B16 tumor cells in collagin-fibrin gels by cytolytic and non-lytic mechanisms

Special Section Guest Editorial: Celebration of the Britton Chance Legacy

Contact Info

Product

Resources

About