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Turning T cells on: Switch Stimulates Tumor Removal

Dec 12, 2013 9:25:32 AM / by Maria

Independent study uses peripheral blood mononuclear cells (PBMCs) from HemaCare to investigate co-stimulatory molecules to effector T cells.

 

Dr Garnet-Benson and her team of researchers from Georgia State University recently published their findings in the Journal of ImmunoTherapy of Cancer Research about "Turning On T Cells".[1]

Cytotoxic T cells,  T cells which destroy tumor cells, effectively recognize specific cell surface antigens that mark cancerous cells for removal. However, tumor cells have cleverly developed mechanisms for evading recognition by immune response - they suppress the signals that stimulate cytotoxic T cell recognition!

Fortunately radiation doses used in cancer therapy induces cytotoxic T cells to destroy tumor cells. Irradiation actually causes cellular damage and several transcriptionally regulated pathways are up-regulated as a consequence, including DNA damage response and apoptotic proteins.  Interestingly, two important co-stimulators for killing by cytotoxic T cells, OX40 ligand and 41BB ligand, are also activated by irradiation in tumor cells.

In order to understand the molecular mechanisms of how irradiation up-regulates the expression of the genes that code for OX40 and 41BB, Garnet-Benson et al., used PBMCs derived from leukapheresis, supplied by HemaCare, and isolated CD8+ T cells a.k.a cytotoxic T cells. The researchers discovered that OX40L and 41BBL are epigenetically regulated and that T cells incubated with tumor cells with up-regulated OX40L and 41BBL showed increased survival, activation and effector activity. In conclusion, the results suggest that radiation can be used to make human tumors more immunogenic through epigenetic modulation of genes that stimulate T cells.

Read more about their findings and access the full publication

Try HemaCare's cryopreserved PBMCs yourself, currently 50% off these and other cell types

References

[1] Kumari, A., Cacan, E., Greer, S.F., and Garnett-Benson, C.  Turning T cells on: epigenetically enhanced expression of effector T-cell costimulatory molecules on irradiated human tumor cells. Journal for ImmunoTherapy of Cancer 2013, 1:17  doi:10.1186/2051-1426-1-17

[2] Effects of CD28 co-stimulation on long-term proliferation of CD4+ T cells in the absence of exogenous feeder cells.  J Immunol. 1997 Dec 15;159(12):5921-30

Topics: Cytotoxic T Cells, PBMCs, peripheral blood mononuclear cells, research, T lymphocytes, tumor cells

Maria

Written by Maria

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