Pancreatic cancer patients may benefit from future precision treatments as a new study shows how some tumours may potentially be more susceptible to macrophage-based therapies.
The findings suggest that some tumour cells are more likely to be infiltrated by T cell treatments, while others had myeloid cell infiltration.
This means that cells such as macrophages could be suitable for future immunotherapeutic treatments in some cases.
Using cells from twelve patients, the research team created a single cell map of tumour infiltrating immune cells and peripheral immune cells, coupled with gene expression, single cell TCR and BCR sequencing and identifying proteins expressed on these cells.
The team then verified their findings using two other large publicly available pancreatic cancer datasets.
Dr Shivan Sivakumar is Associate Professor of Oncology from the University of Birmingham and lead author of the study.
The researcher said: “Pancreatic cancer is a tumour that does not respond to existing immunotherapies (checkpoint inhibitors).
“A basis for this is that there is not the same immunogenic reaction to the tumour that exists in other cancers.
“We therefore mapped out how the immune system is constructed in pancreatic cancer patients.
“This has helped us understand with a high degree of confidence what immune cells are present in pancreatic cancer and let us see how the tumour evades the immune system.
“We demonstrate the need for trials to assess changes in immune infiltration over time.
“Collectively our data provides a foundation for understanding the failure of immunotherapy in pancreatic cancer with an avenue for designing novel therapeutics and tailored interventions.
Rachael Bashford-Rogers is Associate Professor of Molecular and Cellular Biochemistry from the University of Oxford and a senior author of the study.
She said: “We have uncovered distinct immune environments in pancreatic cancer, revealing new therapeutic opportunities to improve outcomes for this deadly disease.
“By leveraging single-cell multi-omics and novel computational approaches, this study identifies potential strategies such as boosting certain cell responses, and depleting suppressive immune cells to enhance immune-based treatments.”
The study has also uncovered the important understanding about the role of specific immune cells, such as activated regulatory T cells (Tregs) and B cells, in the immunopathology of this disease.
The team have found that these cells could help to distinguish patients that may benefit from targeted treatments that activate the existing immune response in the tumour area (rich in B and T cells) versus those that have a highly suppressive tumour environment (rich in myeloid cells).
Tackling these cells would play an important therapeutic strategy in the future against pancreatic cancer.
