Cancer is often reduced to genetic changes in individual cells. However, this view is too limited. Tumours do not develop in isolation, but in interaction with their biological environment. How a tumour arises, grows and responds to therapy is decisively influenced by its tumour microenvironment.

We explain what the tumour microenvironment actually is and why it plays a central role in modern cancer research. We also discuss how this concept has changed our understanding of cancer and what consequences arise from it.

Tumour Microenvironment

Why Is It Now in Focus?

The systematic study of the tumour microenvironment is the result of a fundamental shift in perspective in oncology.

As early as the 19th century, Stephen Paget formulated the so-called “Seed and Soil” hypothesis. It states that tumour cells can only grow if they encounter a suitable environment (Paget, 1889).

For many decades, however, a cell-centred approach dominated. Only with advances in molecular biology and immunology from the 2000s onwards — and even more strongly since the 2010s — has it become increasingly clear that tumours actively interact with their environment and deliberately modify it (Hanahan & Weinberg, 2011; Hanahan & Coussens, 2012).

What Exactly Is the Tumour Microenvironment?

This environment refers to all cells, structures and signalling substances that surround a tumour and influence its behaviour.

These include:

·       immune cells (e.g. T cells, macrophages)

·       fibroblasts

·       blood and lymphatic vessels

·       extracellular matrix

·       signalling molecules such as cytokines and growth factors

These elements form dynamic systems that actively influence tumour growth (Quail & Joyce, 2013)

How Do Tumours and Microenvironments Influence Each Other?

Although one cannot assume that a tumour microenvironment “intends” to promote tumour growth, it is actively modified by tumour cells — and does so.

Key mechanisms include:

·       promotion of (abnormal) blood vessel formation

·       adaptation of tissue structures to the needs of the tumour

These processes enable tumours to establish themselves and to spread further (Hanahan & Coussens, 2012).

But that is not all, because the immune system is a central component of the tumour microenvironment ...

The Tumour and the Immune System

Under normal conditions, the immune system recognises and eliminates abnormal cells. However, tumours can develop mechanisms to evade this control, for example by suppressing immune responses and/or establishing an immunosuppressive environment.

Such an environment can be created by …

·       releasing inhibitory signalling molecules

·       “reprogramming” immune cells

·       blocking signals that would normally trigger a defensive response.

The extent of such processes, which serve the tumour’s self-preservation, can be decisive for the further course of the disease (Fridman et al., 2012).

Tumour Microenvironment: Therapeutically Relevant!

Understanding the tumour microenvironment has direct implications for cancer therapy.

Modern treatments increasingly take into account not only tumour cells themselves, but also their surrounding environment.

Examples:

o   immunotherapies (which specifically activate or modulate the body’s own immune system)

o   interventions in signalling pathways

o   strategies to influence inflammatory processes.

The tumour microenvironment clearly shows that cancer cannot be considered in isolation.

Conclusion: Why the Tumour Microenvironment Is Gaining Attention

Short and simple: the way tumour cells, metabolic processes, tissue structures and immune responses interact is of great importance for disease progression and treatment success.

In our next article, we will therefore take a closer look at Next-Generation Immunotherapies. But first ...

FAQ – Frequently Asked Questions About the Tumour Microenvironment

1. Why do tumours in two individuals with the same diagnosis sometimes respond differently to the same treatments?

Because their tumour microenvironments may differ. Factors such as immune cell activity, blood supply and signalling molecules significantly influence treatment response.

2. Can a tumour even grow without a supportive microenvironment?

Tumour cells may initially undergo transformation, but long-term growth and spread generally depend on a supportive environment.

3. Can changes in the tumour microenvironment influence the risk of metastasis?

Yes, an environment that promotes growth, cell mobility and blood vessel formation can facilitate the spread of tumour cells. The tumour microenvironment therefore also plays a role in the development of metastases.

4. What role does blood supply play within the tumour microenvironment?

Blood supply influences how well a tumour is supplied with oxygen and nutrients. At the same time, it determines how effectively drugs can reach the tumour. Altered or uneven vascular structures can therefore affect treatment response.

Further information on the treatment of cancer can be found in the respective volume of our “Medizinskandale” series as well as in the volumes of our “Codex Humanus.” The fifth volume has recently been published. Feel free to visit our online shop. Also, our other blog articles provide additional insights into these and many other topics.

Sources:

·       Paget, S. (1889): “The distribution of secondary growths in cancer of the breast,” The Lancet.

·       Hanahan, D.; Weinberg, R. A. (2011): “Hallmarks of cancer: The next generation,” Cell.

·       Hanahan, D.; Coussens, L. M. (2012): “Accessories to the crime: Functions of cells recruited to the tumor microenvironment,” Cancer Cell.

·       Quail, D. F.; Joyce, J. A. (2013): “Microenvironmental regulation of tumor progression and metastasis,” Nature Medicine.

·       Fridman, W. H. et al. (2012): “The immune contexture in human tumours: impact on clinical outcome,” Nature Reviews Cancer.