Malignant lymphoma cells can be fended off by our immune system’s natural killer cells, which is why they are considered a promising therapeutic approach.

But there is one problem with the approach. In the direct vicinity of the tumor the natural killer cells lose their effect.

Now, scientists of Helmholtz Zentrum München have now detailed what mechanism blocks the natural killer cells as well as how the blockade could be lifted.

An inflammatory cytokine inactivates NK cells - altered surface molecules block immune activation The scientists identified two key tumor-specific factors associated with impaired natural killer (NK) cell function.

Inflammatory Cytokine

First, a specific inflammatory cytokine (IL-10) is indirectly involved in the inactivation of NK cells. Second, the tumor cells develop protective mechanisms against the NK cells.

The team showed that specific surface molecules of the tumor cells, NKG2D ligands, which NK cells bind to are down-regulated. Consequently, the NK cells lack an important activation mechanism and are no longer able to carry out cytotoxic activity.

Despite the inhibitory strategies of the tumor cells, at an early stage the NK cells produce the cytokine interferon-gamma (IFN-γ), the scientists reported. IFN-γ is essential to activate further immune responses that support the fight against the tumor.

Team leader Dr. Ralph Mocikat, of the Institute of Molecular Immunology (IMI), said:

“Our results show that the transfer of NK cells is a possible strategic option to treat B cell lymphoma. According to our findings, this therapeutic approach can be optimized when transferred NK cells are already activated in vitro prior to their injection, thus bypassing the missing activation potential in the tumor microenvironment. An additional injection of IFN-γ or of antibodies against IL-10 could further support the immune activity."

Belting et al. (2015) Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma. European Journal of Immunology, DOI: 10.1002/eji.201445375

_Photo: Confocal micrograph showing a killer T-cell attacking it’s tumour cell target. The killer cell directs secretory granules granules (red) along microtubules (green) towards the immunological synapse formed between the two cells. The killer cell is distinguished using CD8 (blue), a cell surface marker found on the killer cell, but not the target. Credit: Alex Ritter, laboratory of Professor Gillian Griffiths, University of Cambridge, Wellcome Images _

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