Innovative Mechanism Enhances Immune Response Against Cancer

Recent research has identified a groundbreaking biological mechanism that could significantly improve how the immune system combats cancer. Scientists from the Garvan Institute of Medical Research and UNSW Sydney discovered that a less active form of the gene NOD2, when combined with radiotherapy or immunotherapy, can dramatically amplify the body's ability to attack tumor cells. This discovery sheds light on why some patients exhibit exceptional responses to immunotherapy treatments, such as anti-PD1 checkpoint inhibitors, while others do not.

Immunotherapy, which mobilizes the immune system to target and eliminate cancer cells, has revolutionized cancer treatment over the past decade. Among these therapies, anti-PD1 inhibitors have been widely adopted for treating various cancers including lung, melanoma, and gastrointestinal origins. However, a significant challenge remains—only a subset of patients achieves substantial benefit, and the reasons behind this variability are not fully understood.

To explore this, researchers analyzed a group of Australians with advanced lung cancer who responded remarkably well to anti-PD1 therapies. They found that these individuals were more than twice as likely to carry less active versions of the NOD2 gene, which is involved in immune regulation. Interestingly, these genetic variants appeared to work synergistically with autoimmune responses triggered by the treatment, effectively boosting the immune attack on cancer cells.

The implications of these findings are broad. Not only do they advance our understanding of the genetic factors that influence immunotherapy success, but they also suggest potential for personalized treatment strategies. For example, patients with less active NOD2 genes might be particularly good candidates for combination therapies that further stimulate immune responses.

Moreover, the research confirmed that the NOD2 pathway’s role in enhancing immune responses extends beyond lung cancer, including evidence from colorectal cancer models. This opens avenues for expanding targeted immunotherapy approaches across a variety of cancers.

As Professor Chris Goodnow emphasized, this discovery highlights the complex and interconnected nature of immune mechanisms. It suggests that leveraging multiple genetic pathways could lead to more effective and tailored treatments for cancer patients, ultimately improving survival rates and quality of life. The ongoing research aims to better predict which patients are likely to respond favorably to immunotherapy, paving the way for more personalized and successful cancer treatments.

Source: https://medicalxpress.com/news/2025-08-newly-mechanism-supercharge-immune-cancers.html