In a recent study in mice, researchers found that engineered immune cells were able to shrink tumours and prevent the cancer from spreading to different parts of the body.
Metastasis is the leading cause of death in patients. Despite ongoing advancements in our ability to treat cancer, our understanding of metastatic processes lags behind. Increased understanding of these processes and the metastatic microenvironment will be necessary to develop effective therapies for metastatic disease.
During cancer progression, the primary tumour secretes factors that prime distant sites for metastasis. This specialised microenvironment supports the seeding and outgrowth of disseminated cancer cells – also known as the pre-metastatic niche. The pre-metastatic niche is complex and dynamic. However, our knowledge of the key regulatory signals involved during metastatic progression remain poorly understood.
Engineered immune cells
In this study, published in Cell, researchers sought to explore the behaviour of immune cells in the pre-metastatic niche. The team specifically studied mice implanted with rhabdomyosarcoma, a type of cancer that typically develops in the muscles of children and often spreads to their lungs. They looked at the lungs of these mice after the tumours formed in the leg muscles but prior to the cancers being found in the lungs.
The team found that myeloid cells were abundant in the pre-metastatic niche and continued to gather as the cancer progressed. These cells typically signal and activate their immune cells in the body’s first response to infection, injury and cancer. However, the team found that in the lung pre-metastatic niche these cells were signalling to dampen down the immune response.
As a result, to target this immune suppression program, researchers genetically engineered myeloid cells (GEMy) to deliver IL-12. The team found that these genetically engineered immune cells were able to reverse immune suppression in the pre-metastatic niche by activating antigen presentation and T cell activation. This resulted in reduced metastatic and primary tumour burden, as well as improved survival of tumour-bearing mice. Most importantly, the team found that in combination with chemotherapy, surgery or T-cell transfer therapy, the effects of the GEMy treatment improved.
The team also created GEMy from human cells in the lab, which produced IL-12 and activated cancer-killing immune cells. They hope now to test the safety of these cells in clinical trials.
Image credit: By Mohammed Haneefa Nizamudeen – canva.com