The research, which was presented at the American Association for Cancer Research Annual Meeting in 2024 and published in Cancer Discovery, is a component of the Rubicon project, which attempts to map the immunology of lung cancer in detail in order to expedite the discovery of novel therapies.
The group categorized four distinct environmental categories that are present in the vicinity of lung tumors and are correlated with distinct cancer growth patterns. Cancers that showed high neutrophil counts but poor T and B cell immunological infiltration were more likely to metastasize to other body regions.
Blood vessels, immune cells, cancer cells, and structural proteins make up the tumor microenvironment. To obtain a more realistic picture of the course of the disease, it is useful to examine the tumor and its surroundings from several angles because the composition of the microenvironment might change within and around the tumor.
Through the examination of tumor samples and normal tissue from 81 patients with non-small cell lung cancer (NSCLC) included in the TRACERx project, the researchers were able to map individual cells and delineate four distinct microenvironments in lung cancer.
They examined white blood cells implicated in the immunological response, such as neutrophils, macrophages, and T and B cells. The quantity of immune cells in each class of microenvironment varies depending on the location of the tumor:
- In 28% of tumors, the immune system was very active, with both the inside and outside of the tumor having large concentrations of T and B cells as well as macrophages. They were called “immune hot.”
- In 24 percent of tumors, there was little macrophage and T cell infiltration in the inner region, but there was a high concentration of B and T cells, sparsely populated in the outer region, with few macrophages.
- A less active immune milieu was present in 17% of tumors, with fewer T and B cells as well as macrophages dispersed throughout the tumor.
- In 19% of tumors, there was a high neutrophil count but a low level of T, B, and macrophage infiltration.
The researchers noticed that tumors of the fourth category, which was found to have elevated neutrophil counts, were also situated further from a steady blood supply. These tumors’ subsequent evolutionary alterations allowed them to evade the T and B immune cells, which are capable of attacking the malignancy.
The researchers discovered that tumors with a higher propensity to spread had more neutrophils when comparing tumors that were likely to spread vs those that weren’t. After that, they employed machine learning and statistical techniques to verify this link.
The findings imply that counting neutrophils may be a useful clinical test that aids in identifying patients who may require further care to stop the spread of cancer.
Co-senior author of the paper Mihaela Angelova, a postdoctoral scholar in the Crick’s Cancer progression Laboratory, stated: “We’ve shown that high infiltration of neutrophils could be a marker for cancer evolution and spread. These tumours were genetically altered, separated from the blood supply and managed to evade the immune system, making them better able to spread.”
Professor Charlie Swanton, Chief Clinician at Cancer Research UK, Head of the Cancer Evolution Laboratory at the Crick, and co-senior author of the study from the UCL Cancer Institute, stated: “Lung cancer, particularly if caught at a later stage, is hard to treat, and mapping the environment around the tumour can help us to categorise cancers and work out personalised treatment strategies for patients.”
“This research highlights the importance of pairing the evolutionary history of a tumour with information on how the tumour microenvironment organises in 3D to build the most accurate picture of an individual’s cancer.”
The question that the researchers are currently pursuing is what happens to the tumor microenvironment as the cancer spreads and changes genetically across the body.