The investigators underscored that 50% of patients who undergo anti-PD-1 therapy for advanced cSCC do not respond to treatment, requiring increased research into potential mechanisms of therapeutic resistance and predictive biomarkers.
Pre-treatment cSCC tumor samples were used for whole-transcriptome profiling, and the authors evaluated treatment outcomes and clinical data in association with gene expression.
Certain elevated gene expressions correlated with inferior response to treatment and early disease progression, including SLC7A5 and SOX2.
The investigators evaluated the same genes at the protein level and found that SOX2 was associated with “a more heterogeneous pattern,” with higher gene expression in tumor samples from patients with cSCC progression.
The study authors underscored that their research was “hypothesis-generating” and identified potential candidate predictive biomarkers for response to anti-PD-1 therapy in patients with advanced cSCC.
A team of researchers from Germany conducted the study and published their findings in Cancer Immunology, Immunotherapy.
The investigators underscored that 50% of patients who undergo anti-PD-1 therapy for advanced cSCC do not respond to treatment, requiring increased research into potential mechanisms of therapeutic resistance and predictive biomarkers.
Pre-treatment cSCC tumor samples were used for whole-transcriptome profiling, and the authors evaluated treatment outcomes and clinical data in association with gene expression. Furthermore, the authors evaluated differentially expressed genes in association with therapeutic response.
To identify “promising targets,” the investigators further analyzed potential targets “at the protein level via immunofluorescence and immunohistochemistry.”
According to the results, tumor samples from patients with cSCC who responded to treatment demonstrated “a distinct immune-active transcriptional profile.” The study authors observed that “interferon-associated signaling, enhanced antigen presentation pathways, and cytotoxic immune activity” characterized the transcriptional profile.
Moreover, various activity signatures were increased in patients who demonstrated superior clinical outcomes, including IFN-γ and cytolytic activity signatures.
“CIBERSORTx-based deconvolution demonstrated marked interpatient heterogeneity, with T cells, macrophages, and NK cells representing major components of the immune infiltrate, but no major differences in overall immune cell composition between patients with early and late/no progression,” the study authors wrote.
Results from the histopathological assessment found that patients who responded to treatment had higher immune cell infiltration. Certain elevated gene expressions correlated with inferior response to treatment and early disease progression, including SLC7A5 and SOX2.
The investigators evaluated the same genes at the protein level and found that SOX2 was associated with “a more heterogeneous pattern,” with higher gene expression in tumor samples from patients with cSCC progression. Higher expression of SLC7A5 was also associated with early disease progression.
The study authors underscored that their research was “hypothesis-generating” and identified potential candidate predictive biomarkers for response to anti-PD-1 therapy in patients with advanced cSCC. They highlighted that these results “require validation in larger independent cohorts.”
