The tumour microenvironment in lung cancer is critical to improving outcomes

Both tumours and the surrounding microenvironments differ greatly.

A new study has found four tumour microenvironments in lung cancer, and each affects the progression of the disease.

Some types of tumour microenvironment have a definite physical barrier, so that immune cells cannot enter the cancer cells, and other types increase the risk of developing metastasis.

The results can strongly affect how lung cancer is treated in the future.

“The tumour microenvironment in lung cancer indicates what type of cancer we are dealing with. By understanding how the microenvironment affects tumour growth, we can improve prognosis and perhaps also develop more targeted treatments in the future,” explains a researcher involved in the study, Mihaela Angelova, Postdoctoral Fellow, Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London, United Kingdom.

The research has been published in Cancer Discovery.

Major differences in tumours

Tumours exhibit considerable heterogeneity. Tumours and the surrounding microenvironment differ between cancer cases, and this can strongly affect how cancer develops, the immune system’s chances of defeating the cancer and which treatment works best.

This can also strongly affect whether the cancer can metastasise, and the tumour microenvironment also strongly influences tumour growth.

The microenvironment comprises cell archetypes that either help tumours grow or try to combat them.

The tumour microenvironment can include various cells from the immune system, cells that form blood vessels or connective tissue cells, and all these cell types determine the cancer’s potential and limitations.

Tumour microenvironment among 81 people with lung cancer

Researchers from the Francis Crick Institute and University College London aimed to determine how cells in the tumour microenvironment affect how cancer develops and how difficult it can be to treat.

The researchers analysed 198 samples of lung cancer tumours from 81 people with early-stage lung cancer from the TRACERx study, led by Charles Swanton and supported by Cancer Research UK.

Using imaging mass cytometry, the researchers were able to characterise the cells in and around the tumours in detail.

“We aimed to both characterise different tumour microenvironments and determine how the microenvironment affects treatment and clinical outcomes. We also aimed to determine how microenvironments can vary within the same tumour. This may indicate whether we can infer anything about the entire tumour by just analysing a small part of it,” says Angelova, adding that, before the study, the researchers had developed the analytical tools required to carry out the studies and analyse the results.

The analytical tools, which are available to researchers worldwide, have been published in Nature Communications.

Four types of tumour microenvironment

The researchers investigated the tumour microenvironment of immune cells: B cells, T cells, macrophages and neutrophils.

This comprehensive characterisation revealed that, broadly speaking, four tumour microenvironment archetypes affect outcomes. Three of these archetypes had been characterised previously – but not the fourth.

The first archetype is dominated by immune cells capable of infiltrating the tumour. In the second archetype, the body’s immune cells are only present in the microenvironment around the tumour but do not infiltrate it.

The third archetype has few immune cells either in or around the tumours. The fourth is peculiar and has a high concentration of neutrophil immune cells in both the tumour and the microenvironment and few other immune cells.

Tumour microenvironment associated with greater risk of metastasis

The researchers then investigated the clinical characteristics of the four tumour microenvironments.

This revealed that, in the second type of tumour microenvironment, in which the cells of the immune system do not infiltrate the tumour but are only present in the microenvironment around the tumour, fibroblast cells frequently appear to form a barrier between the tumour and the surroundings.

This barrier prevents the cells of the immune system from infiltrating the tumour and degrading it from within.

The fourth type of tumour microenvironment, with high infiltration of neutrophil cells, in which immune T cells in particular were absent, was often far away from a blood supply, which is required to recruit immune cells to combat the tumour.

This type of tumour microenvironment with many neutrophil cells also often had better opportunities to metastasise.

Finally, this archetype was also the most homogeneous: samples from two places on the tumour are most likely similar.

“This is good because it can affect how well we can use the tumour microenvironment for arriving at a prognosis or a treatment decision. A person with a tumour with many neutrophils has a high risk of metastasis, and so we probably do not need to take more samples from the same tumour, since it is probably quite homogeneous in all parts of the tumour,” explains Angelova.

May improve treatment

According to Mihaela Angelova, the study indicates how homogeneous or heterogeneous different types of tumours with associated tumour microenvironments are.

It also helps researchers to determine how different types of tumour microenvironments help tumours to spread by evading the immune system.

All this can contribute to better opportunities to make more precise diagnoses and to provide more targeted treatments based on the tumour microenvironment in each individual tumour.

“Our future work will focus on determining what the tumour microenvironment actually does to the tumours on a mechanistic level and how we can use this knowledge to develop better treatments based on the exact tumour microenvironment in their tumour,” concludes Mihaela Angelova.