Eosinophils in Colorectal Cancer: Emerging Insights into Anti-Tumoral Mechanisms and Clinical Implications

Eosinophils are myeloid effector cells whose main homing is the gastrointestinal tract. There, they take part in type I and type II immune responses. They also contribute to other non-immunological homeostatic functions like mucus production, tissue regeneration, and angiogenesis. In colorectal cancer (CRC), eosinophils locate in the center of the tumor and in the front of invasion and play an anti-tumoral role. They directly kill tumor cells by releasing cytotoxic compounds and eosinophil extracellular traps or indirectly by activating other immune cells via cytokines. As CRC progresses, the number of infiltrating eosinophils decreases. Although this phenomenon is not fully understood, it is known that some changes in the microenvironmental milieu and microbiome can affect eosinophil infiltration. Importantly, a high number of intratumoral eosinophils is a favorable prognostic factor independent from the tumor stage. Moreover, after immunotherapy, responding patients usually display eosinophilia, so eosinophils could be a good biomarker candidate to monitor treatment outcomes. Finally, even though eosinophils seem to play an interesting anti-tumoral role in CRC, much more research is needed to fully understand their interactions in the CRC microenvironment. This review explores the multifaceted roles of eosinophils in colorectal cancer, highlighting their anti-tumoral effects, prognostic significance, and potential as a biomarker for treatment outcomes.