Immunity<\/em> on 31 March 2022.<\/p>\nHow does cancer form in the body?<\/h3>\n
Our bodies are capable of naturally clearing cancerous cells \u2013 the immune system typically detects mutated cells in our body and destroys them. However, on occasion, cancerous cells can discover a way to remain undetected from the immune system.<\/p>\n
The cells then develop molecular signals that block immune cells from recognising them as a threat. This, among other strategies, allows cancer cells to multiply and grow into tumours. Understanding the molecular mechanism of this process has resulted in the development of new cancer treatments, called immunotherapies. These treatments encourage the patient\u2019s immune system to target the tumour and limit its growth.<\/p>\n
Unfortunately, current immunotherapies are not effective for all types of cancers \u2013 most cases of colon cancer do not respond to these treatments. However, researchers from DUT have described a new pathway that lets colon cancer hide from the immune system. Their results provide a potential first step towards the development of a new generation of immunotherapies.<\/p>\n
How is this \u2018new\u2019 colon cancer avoiding immunotherapies?<\/h3>\n
Inhibition of immune cells is conducted by special signals present on the surface of cancer cells. \u201cThese signals are known as checkpoint proteins,\u201d explained Professor Sebastian Zeissig, leader of the study, from the University Hospital Dresden and the Centre for Regenerative Therapies Dresden (CRTD) at DUT.<\/p>\n
Current immunotherapies utilise drugs called \u2018checkpoint inhibitors,\u2019 to target a small set of known checkpoint proteins. Unfortunately, this approach had a limited impact on colon cancer growth.<\/p>\n
\u201cThis raised the question of whether there are other checkpoint proteins that may represent more promising targets for immunotherapy in colon cancer,\u201d noted Dr Kenneth Peuker, author of the study.<\/p>\n
Researchers analysed colon cancer samples and investigated the signal proteins present in tumour cells, but not in the healthy tissue. Two proteins were considered note-worthy in this observation: CB7H3 and B7H4. Both were present in large numbers in colon cancer cells, while almost undetectable in the healthy tissue.<\/p>\n
\u201cWe decided to block B7H3 and B7H4 in colon cancer cells,\u201d added Dr Peuker. \u201cThe result was startling. Tumour tissue, in which these signals were disabled showed significantly slowed growth or even shrinking. We have observed that now the immune cells could invade the cancer tissue and started to control tumours cells.\u201d<\/p>\n
Additional tests confirmed that the B7H3 and B7H4 proteins are indeed working as checkpoint proteins. \u201cBlocking these signals suddenly allowed immune system to attack tumours cells,\u201d noted Professor Zeissig.<\/p>\n
Scientists discovered B7H3 and B7H4 to be present, not only in the primary colon cancer tumours, but also in their metastases in the liver. Disabling these proteins slowed the growth of the primary tumours as well as their liver metastases \u2013 researchers observed that some of the treated mice survived long-term despite having metastatic tumours.<\/p>\n