# IFN-gamma in the tumor microenvironment: dual roles in cancer progression and therapy

## TL;DR

IFN-gamma has both beneficial and harmful effects in cancer, making it a complex target for immunotherapy.

## Contribution

The paper highlights the dual role of IFN-gamma in tumor progression and therapy.

## Key findings

- IFN-gamma enhances immune cell activity and inhibits tumor growth.
- Prolonged IFN-gamma exposure can lead to immune resistance and treatment failure.
- Understanding IFN-gamma's mechanisms is crucial for effective cancer therapy.

## Abstract

Interferon-gamma (IFN-γ), as a pleiotropic cytokine, plays a pivotal role in antitumor immunity. Its remarkable immunostimulatory, antiproliferative, and pro-apoptotic effects make it a promising candidate for tumor immunotherapy. Here, we highlight the dual role of IFN-γ in the tumor microenvironment during tumor development and treatment. IFN-γ can enhance antigen presentation, boost cytotoxic T cell and natural killer cell activity, and inhibit angiogenesis, promoting tumor regression and correlating with favorable therapeutic outcomes. However, prolonged exposure may induce the upregulation of immune checkpoint molecules such as programmed death-ligand 1, trigger T cell exhaustion, and recruit regulatory T cells, phenomena associated with the development of treatment resistance in cancer therapy. This dual nature poses significant challenges for harnessing IFN-γ in tumor treatment, necessitating an in-depth understanding of its mechanisms within specific microenvironments. Although numerous studies have explored IFN-γ-based tumor therapies, their outcomes have been inconsistent. Thus, although IFN-γ-based therapeutic strategies hold considerable promise, their clinical translation requires precise modulation to fully exploit its antitumor effects while mitigating potential protumor risks.

See also the graphical abstract(Fig. 1).