Unravelling key processes in colorectal cancer development

CRC ranks third in the list of most diagnosed cancers worldwide. It arises as a consequence of genetic alterations that accumulate over time in the cells lining the large intestine. This ultimately results in their uncontrolled proliferation and malignant transformation. But how do other cells (including immune cells), located within and around a tumour, contribute to CRC onset and development?

“Since studies which clarify the roles of different cells neighbouring tumour cells are scarce, we wanted to shed light on how CRC emerges and progresses by looking beyond just the cancer cell,” says Jessica Roelands, Postdoctoral researcher at the LUMC Department of Pathology.

Turning bad: pioneering tools to decipher CRC

Noel de Miranda, head of the Cancer Immunogenomics group at the LUMC Department of Pathology, explains: “To do this, we used a combination of advanced technologies that allow a much more comprehensive evaluation of the alterations that occur when tissues undergo malignant transformation”. Gene expression  and immune profiles  were evaluated in a spatial context – that is: in several regions of the same tissue, that corresponded to different stages of disease. “This information could not be obtained previously due to technical limitations. Now, we are excited to announce that our research group is one of the first to implement such tools to decipher the mechanisms underlying CRC development.”

Substantial changes in the tumour microenvironment

Roelands, de Miranda and colleagues discovered substantial changes in gene expression within tumour cells themselves, as well as in other cells that compose the ‘tumour microenvironment’. “Interestingly, we noticed an early activation of innate immune processes (our first line of defence in immunity) at the start of CRC development,” the postdoctoral fellow notes.

It is important to understand how tumours evade such immune responses which, presumably,  try to deal with the malignant transformation of cells. “Our study also shows that early during CRC progression, the tumour cells adopt a mechanism to avoid specialised cells of the innate immune defence by transmitting ‘do not eat me’-type of signals”. These biological processes could be targeted for early intervention or prevention.

What’s in it for patients?

The Cancer Immunogenomics group, in collaboration with the Department of Gastroenterology, is paving the way for improving the clinical management of patients with early-staged CRC by elucidating key biological processes that drive this disease. “We did this by providing a framework to identify biological processes and molecules associated with CRC development. These serve as measurable indicators – potentially crucial for the timely detection and adequate staging of cancers,” de Miranda notes. 

“Ensuring patients with CRC are well-informed about ongoing developments in this field is also pivotal to us. In collaboration with Fight Colorectal Cancer, we aim to communicate the results of all our studies through social media platforms and lectures that will be co-organised with patient advocacy groups.”

Read the paper in Gut.