CD27 expression is a clinically accessible biomarker for predicting immunotherapy response in melanoma

Area of Science:

• Oncology
• Immunology
• Biomarker Discovery

Background:

• Immunotherapy has revolutionized melanoma treatment, but identifying patients who will respond remains a challenge.
• Current biomarkers for predicting immunotherapy response in melanoma are limited.
• CD27, a member of the tumor necrosis factor receptor superfamily, plays a role in immune regulation.

Purpose of the Study:

• To evaluate CD27 as a predictive and prognostic biomarker for melanoma immunotherapy.
• To compare the efficacy of CD27 with PD-L1 as a biomarker in melanoma patients treated with immune checkpoint inhibitors.

Main Methods:

• Analysis of public transcriptomic datasets and a clinical cohort of advanced melanoma patients.
• Assessment of CD27 mRNA expression using quantitative real-time PCR (qRT-PCR).
• Evaluation of CD27 protein levels using immunohistochemistry (IHC) and multiplex immunofluorescence.
• Receiver operating characteristic (ROC) curve analysis to determine predictive performance (AUC).

Main Results:

• High CD27 mRNA expression correlated with immune checkpoint gene expression, increased immune infiltration, and favorable prognosis.
• CD27 demonstrated strong predictive performance in patients treated with immune checkpoint inhibitors (AUCs ranging from 0.659 to 0.763).
• In a clinical cohort, CD27 mRNA (AUC=0.688) and IHC (AUC=0.656) outperformed PD-L1 (AUC=0.460) in predicting response.
• CD27-positive tumors were associated with significantly longer progression-free survival.
• CD27 was found to be expressed in CD45RO+ memory T cells, indicating its role in anti-tumor immunity.

Conclusions:

• CD27 is a clinically actionable biomarker for predicting response to melanoma immunotherapy.
• CD27 exhibits superior predictive value compared to PD-L1 for identifying responders.
• CD27 positivity is linked to improved clinical outcomes in melanoma patients undergoing immunotherapy.