A digital illustration symbolizing the dual nature of Interferon Lambda in cancer therapy, showing both tumor-suppressing and tumor-promoting aspects.

Interferon Lambda: The Unsung Hero in the Fight Against Cancer?

Theo Raines in Health & Wellness November 2025 • 5 min read.

"Discover how this unique type III interferon could revolutionize cancer treatment by offering a dual role: suppressing tumors and modulating the immune response."

In the ever-evolving landscape of cancer research, a new player has emerged, capturing the attention of scientists and clinicians alike: Interferon Lambda (IFN-λ). As a member of the type III interferon family, IFN-λ shares structural similarities with its better-known counterparts, the type I interferons (IFN-α/β). However, IFN-λ boasts unique biological functions that set it apart, most notably in the realm of tumor suppression. It acts as an antiviral agent, but it's its potential in cancer therapy that's generating excitement.

While IFN-λ activates the same Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways as IFN-α/β, it exhibits a distinctive ability to selectively induce the expression of interferon-stimulated genes (ISGs). This nuanced approach allows IFN-λ to act differently under various physiological and pathological conditions. Specifically, unlike IFN-α/β, IFN-λ doesn't contribute to overstimulation of the immune response or the exacerbation of inflammation.

Yet, as research deepens, unexpected characteristics of IFN-λ are coming to light. It appears that IFN-λ plays a role not only in controlling inflammation but also in promoting immune suppression and, paradoxically, cancer progression under certain conditions. This revelation presents both challenges and opportunities. Understanding these complexities could pave the way for more strategic and effective cancer therapies, moving beyond traditional approaches.

The Dual Role of IFN-λ in Cancer: A Closer Look

A digital illustration symbolizing the dual nature of Interferon Lambda in cancer therapy, showing both tumor-suppressing and tumor-promoting aspects.

The epithelium, a tightly packed layer of cells that forms the body's first line of defense against external threats, is particularly susceptible to infections, inflammation, and cancer. Interestingly, IFN-λ exhibits a preferential expression in epithelial cells, sparking significant interest in its role in viral infections and cancers affecting these tissues. While our knowledge of the IFN-λ system is largely derived from studies on mice and human cell lines, insights are rapidly expanding. Unlike mouse hepatocytes, human hepatocytes are highly sensitive to IFN-λ, hinting at species-specific nuances that require further investigation.

During viral infections in the lungs, IFN-λ is predominantly induced, offering protection without the inflammatory side effects associated with IFN-α. In influenza A virus (IAV) infections, IFN-λ's long-lasting antiviral protection stands out, suggesting its potential as a favored treatment option. However, it's crucial to note that IFN-λ may also induce immune suppression, potentially hindering immune surveillance against infections and cancer.

Direct Antitumor Effects: IFN-λ can directly inhibit cell proliferation and induce apoptosis in tumor cells.
Indirect Antitumor Effects: IFN-λ activates immune cells and inhibits angiogenesis, cutting off the blood supply to tumors.
Immune Cell Activation: IFN-λ can stimulate T cell responses in various cancers, enhancing the body's natural ability to fight tumors.
Angiogenesis Inhibition: IFN-λ has been shown to suppress tumor angiogenesis, further limiting tumor growth and spread.

Conversely, several studies have revealed that IFN-λ can promote tumor progression under certain conditions. For instance, in bladder cancer models, IFN-λ induces the expression of matrix metalloproteinase 9, promoting tumor migration and invasiveness. Similarly, in canine mammary gland cancer, myeloid-derived suppressor cells induce cancer metastasis via IFN-λ production. These findings suggest that while IFN-λ holds promise as a tumor suppressor, it can also act as a cancer promoter, depending on the specific context and stage of cancer development.

The Future of IFN-λ in Cancer Therapy

Since its initial recognition as a potent antitumor agent with limited side effects compared to IFN-α, IFN-λ has emerged as a promising candidate in immuno-oncology. However, the evolving understanding of its dual role in cancer underscores the need for careful consideration and strategic application. By dissecting the mechanisms through which IFN-λ both suppresses and promotes cancer, researchers aim to identify novel molecular and immunological targets that will pave the way for more effective and personalized cancer therapies. This nuanced approach promises to unlock the full potential of IFN-λ, transforming it from a promising agent into a cornerstone of cancer treatment.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1089/jir.2018.0046, Alternate LINK

Title: Interferon Lambda: Toward A Dual Role In Cancer

Subject: Virology

Journal: Journal of Interferon & Cytokine Research

Publisher: Mary Ann Liebert Inc

Authors: Ahmed Lasfar, Andrew Zloza, Ann W. Silk, Leonard Y. Lee, Karine A. Cohen-Solal

Published: 2019-01-01

Everything You Need To Know

How does Interferon Lambda (IFN-λ) differ from other interferons in its effects on the immune system, and why is this significant for cancer therapy?

Interferon Lambda (IFN-λ), a type III interferon, distinguishes itself from type I interferons (IFN-α/β) through its nuanced impact on the immune system. While both activate the JAK-STAT pathways, IFN-λ uniquely induces interferon-stimulated genes (ISGs) expression without the broad inflammatory effects often associated with IFN-α/β. This selective action allows IFN-λ to offer antiviral benefits, especially in epithelial tissues, with reduced risk of immune overstimulation. However, it's vital to note that IFN-λ's effects can vary; it may also induce immune suppression under certain conditions.

What is the dual role of Interferon Lambda (IFN-λ) in cancer, and how does it act as both a tumor suppressor and a promoter?

Interferon Lambda (IFN-λ) exhibits a dual nature in cancer, acting as both a tumor suppressor and, under certain conditions, a promoter. As a suppressor, it directly inhibits cell proliferation, induces apoptosis in tumor cells, activates immune cells, and inhibits angiogenesis. Conversely, it can promote tumor progression by inducing matrix metalloproteinase 9 expression, enhancing tumor migration and invasiveness, and by myeloid-derived suppressor cells inducing cancer metastasis. This complexity requires careful consideration in therapeutic applications.

In what specific tissues and viral infections does Interferon Lambda (IFN-λ) show particular promise, and what are its key mechanisms of action in these scenarios?

Interferon Lambda (IFN-λ) demonstrates preferential expression in epithelial cells, marking its importance in tissues like the lungs. During viral infections, such as influenza A virus (IAV) infections, IFN-λ provides long-lasting antiviral protection without the inflammatory side effects associated with IFN-α. Its ability to activate T cell responses and suppress tumor angiogenesis further highlights its therapeutic potential. However, the potential for IFN-λ to induce immune suppression warrants careful monitoring to avoid hindering immune surveillance against infections and cancer.

What are the current research strategies aimed at maximizing the therapeutic potential of Interferon Lambda (IFN-λ) in cancer treatment?

Researchers are exploring several strategies to harness Interferon Lambda (IFN-λ)'s therapeutic potential in cancer. This involves identifying molecular and immunological targets to maximize its tumor-suppressing effects while minimizing its potential to promote cancer progression. Personalized cancer therapies, guided by a deep understanding of IFN-λ's mechanisms, hold promise for transforming it into a cornerstone of cancer treatment. Further studies are needed to fully elucidate the species-specific nuances, especially differences between mouse models and human hepatocytes, to refine these therapeutic strategies.

How does Interferon Lambda (IFN-λ) influence angiogenesis and metastasis in the context of cancer, and what are the implications of these effects?

Angiogenesis inhibition, where Interferon Lambda (IFN-λ) suppresses tumor angiogenesis, deprives tumors of essential blood supply, limiting their growth and spread. However, the induction of matrix metalloproteinase 9 by IFN-λ in some cancers promotes tumor migration and invasiveness. Further complexity arises from myeloid-derived suppressor cells inducing cancer metastasis via IFN-λ production. Understanding these opposing effects is crucial for strategically applying IFN-λ in cancer therapy to maximize benefits and avoid unintended harm.