Eosinophils in Cancer: Mechanisms and machinery for cytotoxicity

Abstract

Cancer is one of the leading causes of death in North America. For this reason, research into novel therapies to combat tumour growth is an area of intense investigation. Traditional treatment modalities for cancer patients, such as radiation and chemotherapy, have enjoyed only moderate success, partially because these treatments non-specifically target dividing cells and consequently are highly toxic to the patient, and also because some cancers are refractory to such measures. Recently, efforts have been focused towards enhancing the patient‘s immune response to the tumour. These "immunotherapy” strategies direct the specific recognition of neoplastic tissues, which confers protection from remaining or recurring tumour cells. Most cancer immunotherapy protocols presently under study are aimed towards enhancing type 1 T helper (Th1) immunity. Eosinophilia. traditionally associated with type 2 (Th2) immune responses, has been described in certain tumours and during cancer immunotherapy. Interestingly, correlations have been drawn between good prognosis for recovery and localized eosinophilia in the area of primary tumour. To date, these findings are controversial, as no in vivo evidence has demonstrated a direct role for eosinophils in mediating tumour damage. This review will first describe various proinflammatory and cytotoxic molecules produced by eosinophils, and suggest possible mechanisms of inducing anti-cancer immunity. Secondly, evidence suggesting the capacity of eosinophils to kill tumour cells will be provided. Although molecules involved in recruiting and activating eosinophils at the site of tumour growth are largely unknown, candidate molecules will be discussed. Furthermore, recent findings in our laboratory will be described which support the concept that eosinophil-activating cancer immunotherapy merits further investigation.