XCL1 as a Potential Biomarker to Predict Durable Response to Anti-PD-1 Treatment in Non-Small Cell Lung Cancer
XCL1 is secreted by activated T and NK cells. It is thought to function by promoting their engagement with antigen-presenting conventional dendritic cells. XCL1 is of increasing interest to academic and pharmaceutical company researchers as a means to promote antitumor immune responses. A recent study showed how XCL1 expression could also be used as an enrollment criterion for cancer immunotherapy, broadening the practical utility of this unusual chemokine.
Clinical researchers from a hospital in Pisa, Italy analyzed the expression of 770 genes involved in immune regulation to search for molecular signatures. These molecular signatures could improve the selection of patients for treatment with immune checkpoint inhibitors. The subjects were 46 non-small lung cancer patients who were treated with pembrolizumab, a monoclonal antibody that binds programmed death 1 (PD-1), 25 of which showed a durable clinical benefit (DCB), with median progression-free survival (PFS) of 30.6 months. The other 21 patients obtained a non-durable clinical benefit (NCB; median PFS 2.8 months). A significant correlation with DCB was observed for upregulation of 13 genes, including several chemokine or chemokine receptors. XCL1 and XCL2 expression, which was 4.3-fold higher in the DCB cohort, had the highest predictive power (AUC = 0.85) for successful pembrolizumab treatment, as shown in the figure comparing several lymphocyte-specific markers with PD-L1 expression, the molecular marker currently used in patient selection.
The study authors conclude: “The PD-L1–based selection of patients for pembrolizumab administration as single agent in first-line setting is not satisfactory. The analysis of immune cell infiltrate can refine the identification of patients likely to achieve a durable clinical benefit. The use of single CD8 T-cell and NK cell markers such as CD8A/B and XCL1/2 could be a simple and effective strategy for clinical practice.”