Immunosurveillance of Virus-induced Tumors

Melief, C. J. M.; Vasmel, W. L. E.; Offringa, Rienk; Sijts, Alice J.A.M.; Matthews, E. A.; Peters, Philipp; Meloen, Rob H.; Eb, A. J. Van Der; Kast, W. M.

doi:10.1101/sqb.1989.054.01.071

Cited by 8 publications

(2 citation statements)

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“…Since tumor cell lines are often stabilized by viruses for permanent growth in vitro it could be argued that virus derived molecules are expressed on the surface of tumor cells [35,36] mediating the contacts and the described effect is not linked to cancer at all. We showed that this possibility is not consistent with our data because primary tumor cells derived from patients suffering from HCC exchanged cytosol with T cells in the same manner.…”

Section: Discussionmentioning

confidence: 99%

Exchange of Cytosolic Content between T Cells and Tumor Cells Activates CD4 T Cells and Impedes Cancer Growth

et al. 2013

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BackgroundT cells are known to participate in the response to tumor cells and react with cytotoxicity and cytokine release. At the same time tumors established versatile mechanisms for silencing the immune responses. The interplay is far from being completely understood. In this study we show contacts between tumor cells and lymphocytes revealing novel characteristics in the interaction of T cells and cancer cells in a way not previously described.Methods/ FindingsExperiments are based on the usage of a hydrophilic fluorescent dye that occurs free in the cytosol and thus transfer of fluorescent cytosol from one cell to the other can be observed using flow cytometry. Tumor cells from cell lines of different origin or primary hepatocellular carcinoma (HCC) cells were incubated with lymphocytes from human and mice. This exposure provoked a contact dependent uptake of tumor derived cytosol by lymphocytes – even in CD4+ T cells and murine B cells – which could not be detected after incubation of lymphocytes with healthy cells. The interaction was a direct one, not requiring the presence of accessory cells, but independent of cytotoxicity and TCR engagement.Electron microscopy disclosed 100-200nm large gaps in the cell membranes of connected cells which separated viable and revealed astonishing outcome. While the lymphocytes were induced to proliferate in a long term fashion, the tumor cells underwent a temporary break in cell division. The in vitro results were confirmed in vivo using a murine acute lymphoblastic leukemia (ALL) model. The arrest of tumor proliferation resulted in a significant prolonged survival of challenged mice. ConclusionsThe reported cell-cell contacts reveal new characteristics i.e. the enabling of cytosol flow between the cells including biological active proteins that influence the cell cycle and biological behaviour of the recipient cells. This adds a completely new aspect in tumor induced immunology.

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Section: Discussionmentioning

confidence: 99%

Exchange of Cytosolic Content between T Cells and Tumor Cells Activates CD4 T Cells and Impedes Cancer Growth

et al. 2013

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“…Results of oncogenes that get initiated promptly in the improvement of tumors can actuate solid provocative reactions. For example, lung tumors in mice that are launched by a transformation in the K-ras oncogene produce chemokines that summon invulnerable cells to the microenvironment of the tumor [3][4][5].…”

Section: Immunogenicitymentioning

confidence: 99%