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The most comprehensive study to date of Hodgkin’s lymphoma, a blood cancer, has provided fascinating insight into what tumor cells must do to survive. Researchers at the Wellcome Sanger Institute have found that cancer cells use signals to attract certain types of immune cells and tell them not to attack them.
Research published in bloodalso found that existing sample data contained high concentrations of these cell clusters, predicting chemotherapy failure. This knowledge can be used to accelerate the transition to precision medicine and identify patients who may benefit from new, more effective immune-based therapies when conventional therapies fail.
Hodgkin’s lymphoma is a cancer of the lymphatic system, an important part of the human immune system that is responsible for fighting infections and destroying abnormal cells. Hodgkin lymphoma is characterized by the presence of Hodgkin/Reed-Sternberg cells, a type of white blood cell called cancerous B lymphocytes. B lymphocytes normally make antibodies that help fight infections.
Hodgkin’s lymphoma is a cancer with approximately 2,100 diagnoses each year in the UK.1Most patients respond well to chemotherapy, radiation therapy, or a combination of both, but there are some who fail these treatments. The good news is that these patients often respond well to new treatments such as “immune checkpoint inhibitors,” especially her PD-1 blockers.2.
In this new study, researchers combined multiple approaches to explore the immune microenvironment around Hodgkin lymphoma tumors in unprecedented detail.
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Single-cell sequencing and spatial transcriptome data from Hodgkin’s lymphoma and healthy lymph node tissue were generated at the Wellcome Sanger Institute to map the genes expressed by each cell and their relationship to their neighbors. pinpointed the position3This was combined with microscopic image data from a Hodgkin lymphoma biopsy at Newcastle University.
Analysis of single-cell data revealed that cancer cells were surrounded by clusters of macrophages, monocytes and cDC2 dendritic cells, all types of immune cells. Imaging data showed that these cells expressed molecules that suppressed their anti-tumor potential.
Ben Stewart, Ph.D., lead author of the Wellcome Sanger Institute study, said: By combining single-cell spatial transcriptome with histological data, we were able to know exactly how Hodgkin’s lymphoma evades an immune response. This approach can be considered a kind of roadmap for molecular pathology that can be applied to other diseases as well. ”
The researchers also noted that there are two different “microenvironments” around cancer cells, giving an indication of how successful conventional treatments are. immune cell clusters were predictive of treatment failure, whereas a microenvironment exhibiting high concentrations of stromal cells was associated with treatment success. Stromal cells indicate that the tissue was previously repaired, so the immune system may already be partially successful in fighting disease. Treatment can help eradicate cancer completely.
Senior author of the study, Chris Carey, Ph.D., of Newcastle University, said: For example, if we could identify which patients had higher concentrations of these immune cell clusters around their tumors, we could tailor treatment to limit the efficacy of chemotherapy in patients less likely to respond to it and avoid immune-based interventions. You can proceed directly to treatment. That’s a better chance. ”
Cellular messages that cancer cells use to manipulate immune cells are also potential drug targets. Interrupting this signaling theoretically allows the immune system to respond as it should and attack cancer cells.
Dr Sam Behjati, senior author of the study, Wellcome Sanger Institute and Cambridge University Hospitals NHS Foundation Trust, said: Combined with other types of data, they can be very specific about what is happening in the human body. I believe it will have a positive impact on ”
reference: Stewart BJ, Fergie M, Young M, et al. Spatial and molecular profiling of mononuclear phagocyte networks in classical Hodgkin’s lymphoma. blood2023: Blood.2022015575. 10.1182/blood.2022015575
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