E61 Tumor-immune system interaction

Topic

The patient's immune system and the tumor maintain a dynamic predator-prey relationship, similar to the one originally described by scientists Alfred Lotka and Vito Volterra for animal populations in the wild: immune system effector cells—primarily cytotoxic T lymphocytes and natural killer cells—act as the predator, while tumor cells act as the prey. Immune effector cells recognize and destroy tumor cells, thereby reducing the tumor population.

However, unlike prey that cannot alter its own defenses, a tumor can develop escape mechanisms that reduce the effectiveness with which immune effector cells recognize and destroy it. The outcome of this tug-of-war—between the immune system's ability to recognize and destroy the tumor and the tumor's ability to develop mechanisms to evade that surveillance—determines whether the tumor is ultimately brought under complete control, remains in a static equilibrium with the immune system, or eventually breaks free to grow autonomously and uncontrollably.

This interplay between the immune system and the tumor is not static; it evolves over time because the pressure exerted by the immune system itself acts as a selective force on the tumor cells: tumor cells that are more easily recognized by the immune system are preferentially eliminated, while those that are less recognizable survive and multiply. Over time, this selection alters the tumor's composition, favoring tumor cell clones that are increasingly invisible to the immune system—a process known as cancer immunoediting.

Cancer immunoediting proceeds through three successive phases. In the first phase, known as elimination, the immune system recognizes and destroys the most immunogenic tumor cells—that is, those most visible and recognizable to it. In the second phase, known as equilibrium, the tumor and the immune system reach a stable coexistence; the immune system continues to contain the tumor without fully eliminating it, while the tumor persists without being able to grow unchecked. In the third phase, known as escape, the tumor cells that survived the pressure of the previous two phases have lost the ability to be recognized by the immune system, leaving the tumor free to grow autonomously and uncontrollably.

Understanding this dynamic relationship between the immune system and the tumor—and specifically identifying which phase of tumor immunoediting a given patient is in—makes it possible to predict whether that patient's tumor is being contained, exists in a state of static equilibrium, or has already escaped immune system control. This also provides the underlying rationale for why treatments that boost immune effector cells—such as those targeting cytotoxic T lymphocytes—can tip this predator-prey relationship back in favor of the immune system.

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