Eosinophils in the tumor microenvironment: implications for cancer immunotherapy

Abstract

Despite being an integral part of the immune response in the tumor microenvironment (TME), few studies have mechanistically elucidated eosinophil functions in cancer outcomes. Eosinophils are a minor population of granulocytes that are mostly explored in asthma and allergic disorders. Their influence on primary and metastatic tumors, however, has recently come to light. Eosinophils’ diverse armamentarium of mediators and receptors allows them to participate in innate and adaptive immunity, such as type 1 and type 2 immunity, and shape TME and tumor outcomes. Based on TME cells and cytokines, activated eosinophils drive other immune cells to ultimately promote or suppress tumor growth. Discovering exactly what conditions determine the pro-tumorigenic or anti-tumorigenic role of eosinophils allows us to take advantage of these signals and devise novel strategies to target cancer cells. Here, we first revisit eosinophil biology and differentiation as recognizing eosinophil mediators is crucial to their function in homeostatic and pathological conditions as well as tumor outcome. The bulk of our paper discusses eosinophil interactions with tumor cells, immune cells—including T cells, plasma cells, natural killer (NK) cells—and gut microbiota. Eosinophil mediators, such as IL-5, IL-33, granulocyte–macrophage colony-stimulating factor (GM-CSF), thymic stromal lymphopoietin (TSLP), and CCL11 also determine eosinophil behavior toward tumor cells. We then examine the implications of these findings for cancer immunotherapy approaches, including immune checkpoint blockade (ICB) therapy using immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy. Eosinophils synergize with CAR T cells and ICB therapy to augment immunotherapies.

Easily applicable predictive score for MPR based on parameters before neoadjuvant chemoimmunotherapy in operable NSCLC: a single-center, ambispective, observational study

“…Eosinophils are a minor population of granulocytes that are more frequently explored in asthma and allergic disorders. Nonetheless, eosinophils infiltrate multiple solid tumor types and modulate tumor progression either directly by interacting with tumor cells or indirectly by shaping the tumor microenvironment 53 , 54 . Across various types of cancer, several authors have demonstrated an association between blood eosinophils and ICI antibodies, however, the data exist in NSCLC was limited.…”

Exploring the role of innate immunity in Cholangiocarcinoma: implications for prognosis, immune infiltration, and tumor metastasis

“…Innate immune effectors, encompassing natural killer (NK) cells, eosinophils, basophils, and phagocytic cells, play a pivotal role in tumor suppression through direct cytotoxicity against malignant cells or by eliciting adaptive immune responses. The functionality of the adaptive immune system relies on lymphocytes (B and T cells); B cells primarily contribute to humoral immune responses, whereas T cells participate in cellular immune responses [38][39][40][41]. Owing to the initiating and regulatory roles of the innate immune pathway in adaptive immune reactions, exploring its correlation with immune cell infiltration in cholangiocarcinoma is crucial.…”

Regression of metastatic malignant melanoma with dupilumab: A case report

“…The role of eosinophilia in peripheral blood and metastatic tissue of cutaneous melanoma has been controversial; eosinophils express PD-1 and its ligand PD-L1, but the anti-or pro-tumourigenic role of those eosinophils is cancer-specific and may have opposite effects in various types of metastatic tumours through their effect on other immune cells to promote or suppress tumour growth. 25 However, the underlying…”

“…The role of eosinophilia in peripheral blood and metastatic tissue of cutaneous melanoma has been controversial; eosinophils express PD‐1 and its ligand PD‐L1, but the anti‐ or pro‐tumourigenic role of those eosinophils is cancer‐specific and may have opposite effects in various types of metastatic tumours through their effect on other immune cells to promote or suppress tumour growth. 25 However, the underlying immune dysfunction in some human diseases can be ascribed to a lack of appropriate balance between Th1, Th2, and Th17 immune responses, including allergic inflammation, fibrosis, with some autoimmune diseases and cancers showing a predominance of Th2 immunity. 10 Further studies to examine a potential role and mechanism for dupilumab in modulating metastatic malignant melanoma may therefore be justified.…”