Study: Immune cells can be stimulated to improve chemotherapy efficacy during pancreatic cancer treatment

Chemotherapy

A new study from Queen Mary University of London has demonstrated that immune cells can be stimulated to form unique structures within pancreatic cancer, allowing researchers to demonstrate an improvement in chemotherapy efficacy in a pre-clinical model.

The study was funded by Cancer Research UK, the Pancreatic Cancer Research Fund, and the Medical Research Council and published in Cellular and Molecular Gastroenterology and Hepatology.

The immune system plays a critical role in the body’s defence against illnesses such as infections, as demonstrated by the recent COVID-19 pandemic. The same immune system is also capable of assisting us in the fight against cancer.

Pancreatic cancer, on the other hand, is distinct in that the pancreatic cancer cells are surrounded by a dense, impenetrable barrier known as the stroma, which frequently prevents immune cells from reaching the tumour.

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As a result, immunotherapies – drugs that harness the body’s immune system to kill cancer cells – have had limited success in treating pancreatic cancer, but are highly effective against other types of cancer, including skin and lung cancer.

Immune cells have been found to aggregate into clusters known as tertiary lymphoid structures (TLS) within the stroma of some patients with pancreatic cancer, which are associated with improved survival outcomes.

TLS, on the other hand, does not develop spontaneously in all patients with pancreatic cancer. With this in mind, the team set out in this study to investigate the structure and function of TLS in pancreatic cancer and to assess their antitumor activity.

The team conducted an analysis of tissue samples donated by patients to the Pancreatic Cancer Research Fund Tissue Bank to determine the presence of TLS in human pancreatic cancer. TLS was defined in this study as the presence of tissue zones densely packed with B cells, T cells, and dendritic cells – three cell types that play critical roles in the immune response.

The team discovered that TLS was present in only a third of patients whose samples were analysed by using specialised staining techniques to visualise the various cell types present in the samples.

The team created a preclinical pancreatic cancer model to study the development of TLS in pancreatic cancer. TLS was not initially present in the model; however, following injection of two signalling proteins (dubbed lymphoid chemokines) into the mice’s tumours, B cells and T cells infiltrated the tumour site and formed TLS. TLS induction may enhance the efficacy of chemotherapy.

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The team then combined the chemokine injection with the administration of gemcitabine, a type of chemotherapy that is frequently used to treat pancreatic cancer patients. In mice, the combination of gemcitabine and chemokine injection resulted in smaller tumours, an effect that neither treatment could achieve alone.

The study’s lead author, Hemant Kocher, Professor of Liver and Pancreas Surgery at Queen Mary University of London and consultant at Barts Health NHS Trust, said: “Pancreatic cancer is classified as a cold tumour, which means that it does not have a large number of immune cells attempting to fight it. We have demonstrated in this study that immune cells can be harnessed and co-assembled into TLS in a pre-clinical model of pancreatic cancer to increase the efficacy of chemotherapy.”

“TLS formation is critical for mounting an anti-tumour response close to the tumour and overcoming the barrier posed by the stroma. These findings suggest that by combining chemotherapy with appropriate immunotherapy to stimulate immune cells in the tumour microenvironment, more personalised treatments for pancreatic cancer may be possible.”

The anti-tumour activity observed in the preclinical model following TLS formation was associated with B cells activating dendritic cells, which is required for the initiation of an immune response. The findings suggest that when lymphoid chemokines are combined with chemotherapy, they may represent a viable therapeutic strategy for inducing an anti-tumor immune response, which may result in improved clinical outcomes.

Due to the fact that this study used a mouse model, additional research is necessary to determine whether the same results can be observed in other experimental models and in humans. The researchers believe that a better understanding of TLS formation will aid in the development of personalised therapies that harness the body’s own immune system’s ability to fight cancer.

source: ANI

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