# The Progress of Ferroptosis of Immune Cells in the Tumor Microenvironment and Its Impact on Tumorigenesis and Development

## TL;DR

This paper explores how ferroptosis, a type of cell death, affects immune cells in the tumor environment and how it can be used to improve cancer immunotherapy.

## Contribution

The paper highlights the dual role of ferroptosis in tumor immunity and proposes strategies to enhance immunotherapy by targeting it.

## Key findings

- Ferroptosis can both promote and inhibit tumor growth by affecting immune cell function.
- Inducing ferroptosis in tumor and immunosuppressive cells while protecting effector immune cells may improve immunotherapy.
- Targeting ferroptosis shows promise as a strategy to overcome resistance to cancer treatments.

## Abstract

The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. Ferroptosis is an iron‐dependent form of non‐apoptotic cell death characterized by the accumulation of lipid peroxides. The interplay between ferroptosis and the tumor immune microenvironment significantly influences the outcome of cancer immunotherapy. The study aims to elucidate the dual effects of ferroptosis on cancer progression and immune responses, particularly in the context of enhancing the efficacy of tumor immunotherapy.

An extensive literature review was conducted using PubMed to identify studies related to ferroptosis and immune cells in the TME, emphasizing translational research outcomes published within the last 5 years.

The study reviews the literature on the mechanisms of ferroptosis and its interactions with various components of the TME, including immune cells such as CD8+ T cells, dendritic cells, natural killer cells, regulatory T cells, myeloid‐derived suppressor cells, and tumor‐associated macrophages. It also examines the impact of ferroptosis inducers and inhibitors on these interactions, alongside the potential synergistic effects of combining ferroptosis induction with current immunotherapies. Ferroptosis plays a dual role in the TME by both promoting and inhibiting tumor growth through its effects on immune cell function. Activation of ferroptosis in tumor cells can enhance the immunogenicity of cancer cells, thereby improving the effectiveness of immunotherapies. Conversely, ferroptosis in immune cells can lead to immune cell dysfunction and contribute to immunotherapy resistance. The study identifies several therapeutic strategies that harness the induction of ferroptosis to overcome resistance to immune checkpoint inhibitors and enhance the anti‐tumor immune response. Inducing ferroptosis in tumor cells and immunosuppressive cells, while preventing ferroptosis in effector immune cells, emerges as a promising strategy to enhance the efficacy of immunotherapy.

This review highlights the potential of targeting ferroptosis as a sensitization approach to improve cancer treatment outcomes, underscoring the need for further research to fully understand the regulatory mechanisms of ferroptosis in tumor immunity.

The interplay between ferroptosis and the tumor immune microenvironment significantly influences the outcome of cancer immunotherapy. Inducing ferroptosis in tumor cells and immunosuppressive cells, while preventing ferroptosis in effector immune cells, emerges as a promising strategy to enhance the efficacy of immunotherapy. This review highlights the potential of targeting ferroptosis as a sensitization approach to improve cancer treatment outcomes, underscoring the need for further research to fully understand the regulatory mechanisms of ferroptosis in tumor immunity.

Highlights ferroptosis's dual role in promoting and inhibiting tumor growth through immune system interactions, affecting immunotherapy outcomes.Identifies ferroptosis induction as a promising strategy to overcome immunotherapy resistance, emphasizing its potential to enhance anti‐tumor responses.Examines ferroptosis's influence on crucial immune cells within the tumor microenvironment, showcasing its complex role in cancer progression and immune response.Suggests targeting ferroptosis as an innovative approach to sensitize cancer treatments, advocating for further research to exploit its full potential in tumor immunity.

Highlights ferroptosis's dual role in promoting and inhibiting tumor growth through immune system interactions, affecting immunotherapy outcomes.

Identifies ferroptosis induction as a promising strategy to overcome immunotherapy resistance, emphasizing its potential to enhance anti‐tumor responses.

Examines ferroptosis's influence on crucial immune cells within the tumor microenvironment, showcasing its complex role in cancer progression and immune response.

Suggests targeting ferroptosis as an innovative approach to sensitize cancer treatments, advocating for further research to exploit its full potential in tumor immunity.