MWC melanoma research makes high impact

This is one of the first studies to identify and characterise the functions of complex stromal cell populations in human tumour infiltrated lymph nodes and was technically challenging to perform.

Co-authored by MWC investigators Dr Jennifer Eom, Dr Saem Park, Dr Anna Brooks and Prof Rod Dunbar, and colleagues from the University of Auckland’s Dunbar Lab, the paper’s findings are likely to have important implications for future research and clinical practice.

Tumours that invade lymph nodes can wreak havoc on immune system

Lymph nodes play a key role in the body’s immune response, and infiltration by tumours is associated with poor patient outcomes.

“[As with other cancers], once melanoma cells develop they metastasise [or spread] to different parts of the body. That's what makes cancer very lethal,” said the study’s co-lead author Dr Jennifer Eom. “And if they manage to get into the lymphatic vessels, they will go to the lymph node. If you find a tumour in the lymph node, that's usually a really negative prognosis factor for the patient.”

Inside lymph nodes, stromal cells act to provide a ‘home’ for T cells (immune cells whose job it is to circulate the body and kill pathogens and tumours). However, if tumour cells enter a lymph node, the crucial dynamic between stromal cells and T cells will be disrupted.

“As the tumour cells invade and grow in the lymph node, they will alter not only the immune cells but also these helping stromal cells that normally provide nice homes for the immune cells,” explained Dr Eom. 

Study sheds light on how cancer affects lymph node stromal cell function

The team of researchers set about investigating the presence and function of stromal cells in human lymph node tissue. There has been a lack of knowledge about human lymph node stromal cells, despite the important role these cells are known to play in the immune system, and the current understanding of lymph node immune responses is largely based on mouse models.

“[The lack of human tissue research in the literature is] what prompted Dr Saem Park to start looking at healthy human lymph node tissue,” said Dr. Eom. “I joined her to look at melanoma-infiltrated lymph nodes – to see how they changed, what sort of markers they expressed, and how are they look in terms of the immune cells.”

With further expertise contributed by colleagues Dr Anna Brooks and Professor Rod Dunbar, they employed sophisticated techniques such as polychromatic flow cytometry and multiplex immunohistochemistry to examine the molecular characteristics of cells and conduct genomic experiments.

The researchers identified different subpopulations of lymph node stromal cells, each having very distinct environment, localisation and molecular characteristics.

“Our genomic analyses suggest that these different type of stromal cell play very different roles,” said co-lead author Dr Saem Park. “One population was more likely involved in mediating immune responses and another was more involved in organising the extracellular matrix. We hope our findings help further studies to investigate these cell types in human cancer tissue.”

“Our findings show how human lymph node stromal cells are different from mouse cells, and therefore our data will provide important information for future studies of stromal cells in cancer.”

Reference:

Eom J, Park SM, Feisst V, et al. Distinctive Subpopulations of Stromal Cells Are Present in Human Lymph Nodes Infiltrated with Melanoma. Cancer Immunol Res. 2020;8(8):990-1003. doi:10.1158/2326-6066.CIR-19-0796