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20 May 2019

Scientists have identified a signalling molecule that helps Hodgkin’s lymphoma to grow.

Researchers at the Max Delbrück Center (MDC) in Berlin have discovered that lymphotoxin-alpha (LTA) helps the cancer to grow unimpeded, by activating genes for immune checkpoint ligands that protect tumour cells from the body's built-in defence system.

Prof Claus Scheidereit and his team worked with Charité-Universitätsmedizin Berlin, as well as with other MDC research groups, to investigate the mechanisms that contribute to the development of Hodgkin's lymphoma. Their findings are published in the journal Blood.

He said scientists have long known that NF-κB, a transcription factor that boosts the activity of certain genes, plays a central role in the disease. Normally, NF-κB resides in the cytoplasm of the cell and is only recruited to the cell’s nucleus when needed.

However, in Hodgkin’s lymphoma cells, NF-κB is permanently located in the nucleus. There, it influences gene activity so that the cells proliferate unchecked and release signalling molecules that encourage lymphocytes into the diseased lymph nodes.

Prof Scheidereit and colleagues tested cell cultures to see which of the molecules produced by Hodgkin’s cells activate NF-κB, identifying just lymphotoxin-alpha (LTA).

An analysis of data from lymph node tissue samples confirmed that Hodgkin’s lymph nodes produce a significant amount of LTA. Conversely, the researchers also showed that inhibiting LTA blocked the NF-κB activity in Hodgkin's lymphoma cells.

Using gene expression analysis they were able to prove that LTA plays a central role in Hodgkin's cells. LTA activates NF-κB and triggers the release of signalling molecules which contribute to the migration of lymphocytes into the lymph nodes, creating a favourable microenvironment for the cancer cells.


Source: von Hoff, L., Kärgel, E., Franke, V., McShane, E., Schulz-Beiss, K.W., Patone, G., Schleussner, N., Kolesnichenko, M., Hübner, N., Daumke, O., Selbach, M., Akalin, A., Mathas, S., Scheidereit, C. (2019) “Autocrine LTA signaling drives NF-κB and JAK-STAT activity and myeloid gene expression in Hodgkin lymphoma”, Blood, available from doi: 10.1182/blood-2018-08-871293

 

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