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24 May 2023

Targeting the tumour environment could improve immunotherapy responses for lymphoma patients, study reveals

Researchers have shown how the cancer lymphoma reprogrammes cells key to our immune responses, leading them to shift to immunosuppressive activity

Lymphoma picture

A new study has revealed how fibroblast cells that are found within lymphoma tumours are inhibitory towards immune cells, also known as T cells, and the action of immunotherapy drugs that stimulate T cells to attack cancer.

The research, published in the Journal of Clinical Investigation, demonstrates the potential to harness these abnormal fibroblasts to help rejuvenate T cells using novel tumour and fibroblast-targeted combination immunotherapy drugs.

Fibroblast cells are a type of cell that play an essential role in maintaining the structure and integrity of our body’s tissues. They are also the gate-keepers of immune responses, providing the highways for rapid immune cell movement and crucially fine-tuning immune cell function. They can be found in a tumour stroma – the environment or surroundings of a tumour made up of various cells.

Diffuse large B cell lymphoma (DLBCL) is an aggressive B cell cancer that is found in patient lymph node tissues and is the most common type of lymphoma. Although there has been encouraging progress in developing immunotherapies for this disease – including CAR-T cell therapies and T cell bispecific antibodies – clinical responses are still suboptimal for many patients.

The researchers found that cancerous B cells reprogram lymph node fibroblasts, causing a shift from immune-supportive to immunosuppressive activity. This contains important implications on how lymphoma escapes the action of immune cells that should attack cancer – as well as potential for optimising future immunotherapy.

Lymphoma-exposed fibroblasts were shown to hinder T cell and CAR-T cell migration and suppress anti-cancer CD8+ T cell function in an antigen-specific manner. Importantly, the work demonstrates the potential to harness fibroblasts within these tumours, by exploiting the increased expression of the fibroblast activation protein (FAP) in the stromal compartment using FAP-targeted agonist drugs – including a bispecific antibody-like fusion protein.

This pre-clinical science study opens up the prospect of combining stroma (FAP)-targeted therapy to improve the activity of current immunotherapies, such as T cell bispecific antibodies.

we believe this paper describes translationally relevant data that provides important knowledge on how lymphoma avoids being detected by the immune system in patients. Encouragingly, our study identifies a novel treatment approach that could improve immunotherapy responses for cancer patients.”

Dr Alan G. Ramsay, Reader in Lymphoma Biology, School of Cancer & Pharmaceutical Sciences

In this story

Alan  Ramsay

Reader (Associate Professor) in Lymphoma Biology