Imagine an army of tiny soldiers, specifically engineered bacteria, fighting cancer cells from within. That’s the exciting potential of bacterial immunotherapy. While we’ve known about this potential for a while, fully harnessing its power depends on understanding exactly how these bacteria work their magic. How do they manage to slip past our body’s defenses while simultaneously boosting our immune system’s attack against tumors? Our research has uncovered a fascinating mechanism that explains this dual action.

It all boils down to a specific receptor called the interleukin-10 receptor (IL-10R). This receptor plays a crucial role in how our immune system responds to threats, and its behavior within the tumor environment is key. We found that immune cells inside the tumor develop an interesting characteristic: they start expressing high levels of IL-10R, a state we call IL-10Rhi. This change isn’t just a random occurrence; it’s a critical piece of the puzzle in how bacterial immunotherapy works.

Here’s how the engineered Salmonella bacteria take advantage of this IL-10Rhi state:

• Boosting helpful immune cells: The bacteria stimulate tumor-associated macrophages, a type of immune cell, to produce interleukin-10 (IL-10). While sometimes considered an anti-inflammatory signal, in this context, IL-10 actually helps amplify the anti-tumor response.
• Evading the enemy: Tumor-associated neutrophils, another type of immune cell, are usually responsible for engulfing and destroying bacteria. However, the increased IL-10 levels resulting from the IL-10Rhi state hinder the neutrophils’ ability to phagocytose (eat) the bacteria, allowing the Salmonella to survive within the tumor.
• Re-energizing exhausted T cells: Perhaps most importantly, the bacteria, combined with the increased IL-10, reactivate exhausted CD8+ T cells. These T cells are vital for fighting tumors, but within the tumor microenvironment, they often become inactive or “exhausted.” The bacteria effectively wake them up and boost their ability to destroy cancer cells.

This combined effect is incredibly powerful. In our studies, we observed not only tumor elimination but also prevention of recurrence and metastasis across various cancer types. This means the bacteria were not just fighting the existing tumor; they were also preventing the cancer from spreading and coming back later.

Even more exciting, our analysis of human tumor samples suggests that this IL-10Rhi state might be a common feature across various human cancers. This implies that the mechanism we’ve uncovered could be relevant for a broad range of tumor types, opening doors for new and improved cancer therapies.

This discovery unlocks a critical understanding of how bacterial immunotherapy tackles the complex challenge of solid tumors. By understanding how these bacteria manipulate the tumor microenvironment, particularly through the IL-10R pathway, we can develop even more effective strategies to fight cancer using these tiny but mighty microbial allies. This provides a valuable framework for future research focused on modulating the immune response within the tumor to achieve better outcomes for cancer patients.