Mathematical modelling of conjugate formation by cytotoxic lymphocytes and tumour cells

Mathematical modelling of the response of tumour cells to radiotherapy

Nuclear Instruments and Methods in Physics Research Section B Beam Interactions with Materials and Atoms ◽

10.1016/s0168-583x(01)01096-5 ◽

2002 ◽

Vol 188 (1-4) ◽

pp. 210-215 ◽

Cited By ~ 18

Author(s):

N.F. Kirkby ◽

N.G. Burnet ◽

D.B.F. Faraday

Keyword(s):

Mathematical Modelling ◽

Tumour Cells

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Pleiotropic Effects of IL-2 on Cancer: Its Role in Cervical Cancer

Mediators of Inflammation ◽

10.1155/2016/2849523 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 8

Author(s):

Arturo Valle-Mendiola ◽

Adriana Gutiérrez-Hoya ◽

María del Carmen Lagunas-Cruz ◽

Benny Weiss-Steider ◽

Isabel Soto-Cruz

Keyword(s):

Cervical Cancer ◽

Lymphocyte Proliferation ◽

Tumour Cells ◽

Cytotoxic Lymphocytes ◽

Malignant Cells ◽

Normal Lymphocyte ◽

Effector Cells ◽

Current Review ◽

Cervical Cancer Cells ◽

Stat Pathway

IL-2 receptor (IL-2R) signalling is critical for normal lymphocyte proliferation, but its role in cervical cancer is not fully understood. The receptor is composed of three chains: IL-2α, IL-2β, and IL-2γ. Intracellular signalling is initiated by ligand-induced heterodimerization of the IL-2βand IL-2γchains, resulting in the activation of multiple intracellular kinases. Recently, IL-2R was shown to be expressed on nonhaematopoietic cells, especially on several types of tumour cells. However, the function of this receptor on malignant cells has not been clearly defined. The expression of IL-2R and the production of IL-2 in cervical cancer cells have been documented as well as expression of molecules of the JAK-STAT pathway. In the current review we have highlighted the differences in the responses of molecules downstream from the IL-2R in normal lymphocytes and tumour cells that could explain the presence of tumour cells in an environment in which cytotoxic lymphocytes also exist and compete and also the effect of different concentrations of IL-2 that could activate effector cells of the immune system cells, which favour the elimination of tumour cells, or concentrations that may promote a regulatory microenvironment in which tumour cells can easily grow.

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Analysis of B-lymphoma growth, stabilization and regression. A mathematical modeling for the interaction between cytotoxic lymphocytes and tumour cells

European Journal of Cancer and Clinical Oncology ◽

10.1016/0277-5379(91)91262-h ◽

1991 ◽

Vol 27 ◽

pp. S34

Keyword(s):

Mathematical Modeling ◽

Tumour Cells ◽

Cytotoxic Lymphocytes ◽

B Lymphoma

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Identification of the BCL2/adenovirus E1B-19K protein-interacting protein 2 (BNIP-2) as a granzyme B target during human natural killer cell-mediated killing

Biochemical Journal ◽

10.1042/bj20091073 ◽

2010 ◽

Vol 431 (3) ◽

pp. 423-431 ◽

Cited By ~ 10

Author(s):

Gina B. Scott ◽

Paul A. Bowles ◽

Erica B. Wilson ◽

Josephine L. Meade ◽

Boon Chuan Low ◽

...

Keyword(s):

Natural Killer Cell ◽

Natural Killer ◽

Nk Cell ◽

Granzyme B ◽

Killer Cell ◽

Tumour Cells ◽

Cytotoxic Lymphocytes ◽

Interacting Protein ◽

Infected Cells ◽

Adenovirus E1b

Cytotoxic lymphocytes eliminate infected cells and tumours via the perforin-mediated delivery of pro-apoptotic serine proteases known as granzymes. Granzyme B triggers apoptosis via the cleavage of a repertoire of cellular proteins, leading to caspase activation and mitochondrial depolarization. A simple bioinformatics strategy identified a candidate granzyme B cleavage site in the widely expressed BNIP-2 (BCL2/adenovirus E1B-19K protein-interacting protein 2). Granzyme B cleaved recombinant BNIP-2 in vitro and endogenous BNIP-2 was cleaved during the NK (natural killer) cell-mediated killing of tumour cells. Cleavage required the site identified in the bioinformatics screen and was caspase-independent. Expression of either full-length BNIP-2 or a truncated molecule mimicking the granzyme B cleaved form was pro-apoptotic and led to the caspase-dependent cleavage of BNIP-2 at a site distinct from granzyme B cleavage. Inhibition of BNIP-2 expression did not affect the susceptibility to NK cell-mediated killing. Furthermore, target cells in which BID (BH3-interacting domain death agonist) expression was inhibited also remained highly susceptible to NK cell-mediated killing, revealing redundancy in the pro-apoptotic response to human cytotoxic lymphocytes. Such redundancy reduces the opportunity for escape from apoptosis induction and maximizes the chances of immune-mediated clearance of infected cells or tumour cells.

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