When it comes to cancer, many people call it the “King of Diseases”. Although we have developed a variety of drugs to treat cancer, these drugs are not effective for all patients. Even if the condition is briefly controlled and rerelieved, many patients will eventually return.
A study published online December 11in Nature brings new ideas to cancer treatment. As the authors note in the discussion of the paper, it not only gives us a better understanding of the role of the immune system in cancer, predicting the risk of cancer recurrence, but also promises to lead to new cancer treatments.
The study was based on an intuitive observation that the more immune T cells in the patient’s tumor, the more likely the patient would benefit from cancer immunotherapy. In the paper, the researchers also quantified the number of CD8-positive T-cells in patients with kidney, prostate and bladder cancers, which are the main force in the fight against foreign invaders. They found that if these cells were less than 2.2% of the tumor’s immersion levels, the risk of developing the disease after surgery was four times higher!
With this observation, the question naturally arises: Why are there more immune T cells in some tumors? To answer this question, they analyzed CD8-positive T-cells in the tumor in detail. As expected, many T-cells express high levels of immune checkpoint proteins (e.g. PD-1, TIM3, CTLA4, etc.), indicating that these cells are in a state of “failure” and unable to attack cancer cells.
The more patients with kidney cancer (red) with CD8-positive T-cells, the better their postoperative recovery (Photo: Resources)
To their surprise, however, other T-cells exhibit stem-like activity. These cells are expressed with CD28 and TCF1, which maintain the proliferation of immune cells. In response to this result, the researchers made an image analogy: they point out that, in the usual sense, lymph nodes are the total base of T-cells with stem cell activity. But the findings suggest that outside the base, the immune system also places “front-line command” in the tumor, generating fresh force on the front lines of combat and fighting cancer cells.
In fact, these “front-line command” environments are very similar to lymph nodes — near these cells, researchers have found many antigen-presenting cells (APCs). These cells act like “teachers” and tell immune T cells when to attack and who they are attacking. In kidney cancer samples, these APCs formed many distinct front-line bases with stem cell-active T-cells. In samples of prostate and bladder cancer, the researchers also observed the presence of some bases.
Based on the number of these front-line bases, we can predict whether the prognosis for patients is good or bad (Photo: Pixabay)
The authors of the paper point out that although many patients with kidney cancer have undergone surgery to remove the tumor in theory, a significant proportion of patients will relapse. Now, through the front-line bases established by these immune systems, we can predict which patients do not need additional treatment to avoid overtreatment. We can also predict which patients have a higher risk of cancer recurrence and require more frequent testing and intervention.
In addition, the authors note that the findings could provide new insights into cancer immunotherapy. In the past, we thought that T-cells in tumor microenvironments did not work primarily because of the immune-spot proteins expressed on their surfaces, as well as the PD-L1 molecules produced by tumors. But the authors suggest that this may also be because CD8-positive T cells with stem cell activity cannot be continuously activated to produce enough T-cells to fight. If new treatments are developed for this discovery, it could be expected to make cancer treatment more effective.