Eosinophils are a type of white blood cell produced in the bone marrow, primarily recognized for their function in combating certain parasitic infections and their participation in allergic reactions. These cells circulate in the bloodstream for short periods before settling into tissues, where they modulate inflammatory responses. However, research has uncovered a more complicated role for eosinophils, revealing a complex relationship between these immune cells and cancer. This connection is multifaceted, with eosinophils acting as both friend and foe in the context of malignancy.
The Meaning of High Eosinophil Counts
A high count of eosinophils in the blood, a condition termed “eosinophilia,” can be an important finding in a medical evaluation. Eosinophilia is not a disease but a signal that an underlying condition is causing the body to produce more of these cells. While cancer is a possible cause, elevated eosinophil levels are more frequently associated with non-cancerous conditions like allergic disorders, parasitic infections, and certain autoimmune diseases.
The link between high eosinophil counts and cancer often manifests as a “paraneoplastic syndrome.” This occurs when a tumor secretes substances that stimulate the bone marrow to overproduce eosinophils as a reaction to the malignancy. The types of cancers most frequently associated with paraneoplastic eosinophilia include blood cancers like Hodgkin lymphoma and certain leukemias. It is also seen with some solid tumors, including those of the lung, kidney, and cervix.
Eosinophils as a Component of Cancer
Beyond being a systemic reaction to a tumor, eosinophils can be a primary component of the cancer itself, a distinct scenario from paraneoplastic eosinophilia. One such condition is Hypereosinophilic Syndrome (HES), which is defined by persistently high eosinophil levels for over six months that lead to organ damage. In some instances, HES can be a precursor to or a feature of a myeloproliferative neoplasm, a type of blood cancer.
HES may progress into chronic eosinophilic leukemia (CEL), a rare cancer where the eosinophils are part of the malignant clone of cells. In CEL, the uncontrolled proliferation of eosinophil precursors in the bone marrow leads to extremely high numbers of these cells in the blood and tissues. Another concept is Tumor-Associated Tissue Eosinophilia (TATE), which describes the significant infiltration of eosinophils directly into and around a solid tumor mass. This localized accumulation is a feature of certain cancers, such as those of the colon and esophagus.
The Dual Role of Eosinophils in Cancer Progression
Once present within a tumor’s environment, eosinophils can behave in two opposite ways, either helping the body fight the cancer or helping the cancer grow. Their actions depend on the specific signals and factors they encounter within the tumor microenvironment.
On one hand, eosinophils possess anti-tumor capabilities. They contain granules filled with toxic proteins, such as major basic protein, which they can release to kill cancer cells directly. Eosinophils also play a role in coordinating a broader immune attack by secreting signaling molecules called chemokines that recruit other immune cells, like CD8+ T cells, to the tumor site.
Conversely, the same cells can be co-opted by the tumor to support its survival and spread. Eosinophils can release factors that promote the formation of new blood vessels, a process called angiogenesis, which supplies the tumor with oxygen and nutrients. In some contexts, they can also suppress the activity of other immune cells that would normally attack the cancer, effectively shielding the tumor from destruction.
Eosinophils in Cancer Diagnosis and Treatment
The behavior of eosinophils has direct implications for cancer diagnosis and treatment. The presence of these cells within a tumor, or TATE, is increasingly used as a prognostic marker to help predict a patient’s outcome, though its meaning varies significantly by cancer type.
In some malignancies, such as colorectal and gastric cancer, a high level of TATE is associated with a better prognosis and longer survival. This suggests that in these cancers, the anti-tumor functions of eosinophils are dominant. In contrast, for other cancers like Hodgkin lymphoma, high eosinophil infiltration can be a negative prognostic marker linked to a poorer outcome. This understanding is paving the way for new therapeutic strategies, with research into treatments designed to either enhance the tumor-killing abilities of eosinophils or block their tumor-promoting signals.