Eosinophil Dynamics in Cancer Immunotherapy

Eosinophils, traditionally recognised for their roles in allergic and parasitic responses, have emerged as versatile modulators of antitumour immunity. Within the tumour microenvironment, these granulocytes can influence vascular remodelling, antigen presentation and T-cell activation. Under immune checkpoint blockade and other immunotherapeutic modalities, systemic and intratumoural eosinophil counts frequently change, reflecting both therapeutic efficacy and the risk of immune-related adverse events. Mechanistic studies reveal that cytokines such as interleukin-5 and interleukin-33 drive eosinophil mobilisation and tumour infiltration, where eosinophils support CD8+ T-cell recruitment and activation. Conversely, excessive eosinophil expansion may herald endocrine or pulmonary toxicities. The dualistic nature of eosinophil dynamics underpins their potential as both predictive biomarkers for clinical response and early warning signals for treatment-related toxicity, with implications for patient stratification and therapeutic modulation.

Research from Nature Portfolio

A recent retrospective clinical investigation analysed longitudinal eosinophil counts in patients receiving immune checkpoint inhibitors to identify predictors of secondary adrenal insufficiency. The study demonstrated that absolute eosinophil counts above approximately 200 cells/µL or relative counts exceeding 5.6 percent at pre-onset, alongside a notable rise from baseline, were highly sensitive and specific for impending endocrine toxicity. These findings establish peripheral eosinophil monitoring as an accessible screening tool for early detection of adrenal dysfunction, enabling timely intervention and minimising treatment interruptions.

Eosinophil Dynamics in Cancer Immunotherapy publication trend

The graph below shows the total number of articles in eosinophil dynamics in cancer immunotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Eosinophil: A type of white blood cell containing granules with cytotoxic proteins, involved in immune responses and tissue remodelling.

Immune checkpoint inhibitor (ICI): A class of immunotherapy drugs that block inhibitory receptors or ligands (e.g. PD-1, CTLA-4) to enhance T-cell-mediated tumour killing.

Immune-related adverse event (irAE): Unwanted inflammatory side-effects resulting from off-target immune activation during immunotherapy.

Interleukin-5 (IL-5): A cytokine primarily produced by T helper 2 cells, crucial for eosinophil growth, differentiation and survival.

Interleukin-33 (IL-33): An alarmin cytokine released by damaged cells that can promote eosinophil trafficking to tissues and shape local immune responses.

CD8+ T cell: A subset of T lymphocytes capable of directly killing infected or malignant cells upon antigen recognition.

References

1. Eosinophil and IFN-γ associated with immune-related adverse events as prognostic markers in patients with non-small cell lung cancer treated with immunotherapy. Frontiers in Immunology (2023).
2. IL-5-producing CD4+ T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer. Cancer Cell (2022).
3. A retrospective analysis of eosinophilia as a predictive marker of response and toxicity to cancer immunotherapy. Future Science OA (2020).
4. Eosinophil counts can be a predictive marker of immune checkpoint inhibitor-induced secondary adrenal insufficiency: a retrospective cohort study. Scientific Reports (2022).