IFNγ Gene Signature as a Predictive Biomarker

IFN-γ, as a pivotal driving factor in the expression of programmed death ligand 1 (PD-L1) in both cancer cells and host cells, is also regarded as a potential predictive marker for anti-tumor immune effects. Creative Biolabs provides our clients with an introduction to the theory of IFN-γ gene signaling as a predictive biomarker, aiming to help you better understand and utilize this potential biomarker.

IFN-γ Signaling in Tumors

IFN-γ is a critical cytokine produced by activated T cells, as well as natural killer (NK) and NK T cells. As part of the tumor immune feedback loop, the function of IFN-γ signaling is dual:

IFN-γ can directly upregulate the expression of PD-L1/2 in tumor cells and stromal cells, which activates the PD-1 signaling and subsequently downregulates cytotoxic responses.
IFN-γ can directly upregulate the expression of key immune inhibitory molecule indoleamine 2,3-dioxygenase 1 (IDO1) in the tumor immune microenvironment.

This coordinated positive and negative immune signaling allows tumors to survive and develop in a delicate balance.

Fig 1. IFN-γ is involved in chronic inflammatory manifestations and tumor immune checkpoint inhibition.¹

IFN-γ Gene Signaling as a Predictive Biomarker

Numerous studies have already demonstrated the consistency between IFN-γ and clinical outcomes of tumor intervention, providing key evidence for its role in predicting immune checkpoint blockade (ICB) responses:

Mice with IFN-γ blockade show disrupted immune surveillance and tumor rejection.
Knockdown of IFN-γ receptor impairs anti-tumor response to CTLA-4 in mice.
Patients with IFN-γ gene defects exhibit ineffective anti-CTLA4 response in melanoma.
Melanoma patients with functional loss of IFN-γ signaling molecules JAK1 and JAK2 also resist anti-PD-1 therapy.
IFN-γ signaling characteristics are highly consistent with the corresponding reduction in cell cycle and WNT signaling pathway.

IFN-γ induces a series of target genes and has been developed as a gene expression feature. These selected target gene sequences show strong correlations with ICB response and serve as detectable and traceable prospective biomarkers.

Current Research Status

Title: IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade.

Methodology and Research Objective:

Researchers used RNA extracted from formalin-fixed paraffin-embedded (FFPE) tumor tissue samples to specifically study gene expression in the tumor microenvironment. Through rigorous stepwise validation, the predictive correlation between IFN-γ signaling and the clinical response to PD-1 checkpoint blockade was confirmed.

Research Findings:

Active IFN-γ signaling, antigen presentation, cytotoxic effector molecules, and T cell inflammatory microenvironment are common response features of tumors facing PD-1 ICB. A set of focused gene sequences has been identified as predictive biomarkers for the biology of PD-1 ICB response and tumor clinical response.

Correlation between 18 IFNγ Gene Signatures and clinical manifestations of tumors. (Ayers, et al., 2017) Fig.2 Correlation between 18 IFN-γ Gene Signatures and clinical manifestations of tumors.¹

What Creative Biolabs Provide?

Our services transcend theoretical support, encompassing a comprehensive range of immune checkpoint-related solutions. We offer expertise in predictive biomarker identification, assay development, preclinical evaluation, and technical support. From conceptualization to implementation, we are committed to advancing the field of immune checkpoint research and aiding in the development of groundbreaking findings. We cordially invite you to contact us to explore potential opportunities.

Reference

Ayers, Lunceford, et al. "IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade. " The Journal of Clinical Investigation. 7 (2017): 127.

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