Immunotherapy has shown promise in treating various types of cancer, but its effectiveness in colon cancer has been limited. However, recent research has provided new insights into why immunotherapy may fail in some cases.
A study published in Nature Genetics analyzed the effects of immune therapy on mice with DNA mismatch repair deficiency (MMRd), a condition commonly seen in people with colon cancer. It was expected that MMRd would generate new antigens and trigger a positive immune response. Surprisingly, the study found that these tumors were not immunogenic, meaning they did not elicit a strong immune response.
The researchers hypothesized that the diversity of mutations within the tumor cells could be the reason behind the lack of immune response. Unlike tumors with few mutations, which can be compared to a tree with a central trunk, tumors with high tumor mutation burden (TMB) are more like bushes or shrubs with divergent branches. The mutations within these tumors are not shared across all tumor cells, making it difficult for the immune system to recognize and target them.
The study also found that mice with clonal mutations (shared by all cancer cells) were more responsive to immunotherapy than those with subclonal mutations (only shared by a subset of cancer cells). This suggests that similar mutations are more likely to respond to immunotherapy, while diverse mutations may hinder its effectiveness.
According to Anton J. Bilchik, a surgical oncologist and professor of surgery, this research provides valuable insights into why immunotherapy works in some patients but not others. It highlights the heterogeneity of immune cells within a tumor and the potential impact on treatment response.
The findings could lead to more personalized treatment approaches for colon cancer patients. Currently, high tumor mutation burden is used as a metric to qualify patients for immunotherapy. However, the study suggests that other molecular indicators, such as MMRd, may be more informative. Identifying biomarkers that can predict response to immunotherapy would be crucial in improving treatment outcomes.
While this research sheds light on the challenges of using immunotherapy for colon cancer, it also highlights the potential for future clinical studies and a more nuanced understanding of how to treat patients with MMRd, TMB, and colon cancer.
Colorectal cancer is a common type of cancer in the United States, and early detection is crucial for successful treatment. It is recommended that individuals over the age of 45 undergo regular screening, even in the absence of symptoms or risk factors. Various screening methods, such as fecal testing, colonoscopy, or sigmoidoscopy, can be used to monitor and detect precancerous polyps or early-stage cancer.
Immunotherapy has revolutionized cancer treatment, but its application in colon cancer is still evolving. With ongoing research and a better understanding of the factors that influence treatment response, there is hope for increasing the number of patients who benefit from immunotherapy. This study serves as an important step towards that goal.