Harnessing Spatial Biology to Uncover Cell-Cell Interactions in Pancreatic Cancer

Group photo of Joe YEONG Lab

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is one of the most challenging cancers to treat, with survival rates at just 10% over five years. Its aggressive nature, late detection, and resistance to treatments make it a critical focus in cancer research. Recent findings from a team led by Principal Investigator Dr. Joe Yeong provide key insights into how stromal and immune cells interact within the tumour microenvironment, offering new possibilities for improving patient care.
Stromal cells, such as pancreatic stellate cells and cancer-associated fibroblasts, are known to drive chemotherapy resistance and tumour growth. Targeting these cells to return them to a quiescent (resting) state has shown promise in improving outcomes. The team explored how these stromal cells interact with natural killer (NK) cells, vital components of the immune system.

Using multiple techniques across in vitro experiments, murine models, and patient samples, they demonstrated significant bidirectional interactions between stromal and NK cells. Quiescent stromal cells were shown to reduce NK cells’ ability to kill cancer cells. Furthermore, co-culturing these cell types led to major changes in their behaviour and protein activity.

Employing a multiplex spatial biology platform, the researchers analysed NK cell distribution in response to different therapies. In mouse models, NK cells responded differently to chemotherapy alone compared to chemotherapy combined with stromal-targeting agents. In patient samples, closer interactions between NK and stromal cells were associated with long-term survival, highlighting their potential as a prognostic marker.

Lead author Rachel Fincham emphasized the importance of these findings: "Our exciting findings highlight the prognostic implications of stromal-natural killer cell proximity in pancreatic cancer. Taken together, we suggest the potential for spatial biology to be used as a tool for patient stratification in pancreatic cancer."

This research demonstrates the value of spatial biology in uncovering critical details within the tumour microenvironment. By better understanding stromal-immune cell interactions, clinicians may identify patients most likely to benefit from targeted therapies, paving the way for more personalized treatment strategies.

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Harnessing Spatial Biology to Uncover Cell-Cell Interactions in Pancreatic Cancer

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