More knowledge on how immunotherapy works

Medicine and medico technology Health and diseases Cells

Researchers from DTU Health Tech enable improved cancer treatment through increased  knowledge about immunotherapy.

Professor Sine Reker Hadrup and her team at DTU Health Tech have moved our knowledge one step further in this important but complicated area. They have screened a group of patients with bladder cancer, who have been treated with a type of immunotherapy called checkpoint inhibitors, to get further knowledge about what goes on in the body during treatment. The study was conducted by PhD student Jeppe Sejerø Holm in collaboration with Dr. Samuel A. Funts and the clinical team from Memorial Sloan Kettering Cancer Center in New York.

“First and foremost, we have identified T-cells that recognize neoantigens in the blood. Neoantigens are fragments that have emerged from mutations in the patient’s cancer tumour. This means that they are unique for the specific patient, or you could say a personal signature for immunorecognition. And we can see that such T-cells are induced during treatment”, Professor Sine Reker Hadrup explains. 

Accordingly, the T-cells that are specific for the neoantigens are activated after treatment. After three weeks, the T-cell response has increased in most patients, who are responding positively to the treatment. This finding provides the researchers with novel knowledge on how checkpoint inhibition treatment boosts the T cell recognition of cancer cells and can be used to further optimize the treatment strategy.

Towards improved target selection

A better understanding of why only a fraction of the numerous mutations in a cancer tumour become a target for the immune system is another result from this study. In fact, it is only a very small percentage of mutations in the tumour, which are recognised and targeted by the immune system.

“Our study has pinpointed some of the characteristics of the neoepitopes that are recognised by T-cells versus the ones that are not. This is important knowledge for developing an even more focused immunotherapeutic treatment in the future”, Sine Reker Hadrup says.

Mutations in cancer are so diverse and varied that a full understanding will require huge datasets. However, the present work, which includes the to date largest cohort of patients, who have received checkpoint inhibitors, achieves detailed information on neoantigen recognition. This can bring the research community another big step forward.

Patient selection tool

Lastly, the professor and her group have shown that the characteristics of the patient’s cancer tumour before treatment gives indications about the patient’s immune response, i.e., the likelihood that the patient will generate a strong immune response and have positive effects from the treatment. Such knowledge can help medical professionals choose the best type of treatment for each patient.

“This finding is important because we can use this knowledge to predict which patients will have a strong immune response. Such knowledge can be used in the future to guide the treatment decisions related to selecting the therapies most likely to benefit a certain patient group, while minimizing side effects”, Sine Reker Hadrup concludes.

Read the full paper published in Nature Communications.


Checkpoint inhibitors

Immune checkpoints are a normal part of the immune system. Their role is to prevent our  immune system from overreacting, and hence destroys healthy cells in the body.

Immune checkpoints engage when proteins on the surface of immune cells called T cells recognize and bind to partner proteins on other cells, such as some tumour cells. These proteins are called immune checkpoint proteins. When the checkpoint and partner proteins bind together, they send an “off” signal to the T cells. This can prevent the immune system from destroying the cancer. Immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This prevents the “off” signal from being sent, allowing the T cells to kill cancer cells.