(A536) Drug Concentrations of Anti-EGFR Therapy Correlate with Immune-active Microenvironments in Human Tumor Specimens

Introduction: Anti-EGFR therapy has failed to provide significant benefits to patients with head and neck squamous cell carcinoma (HNSCC) as a monotherapy. Evidence in other tumor types suggests that anti-EGFR therapy promote immunomodulatory changes which may create a tumor microenvironment (TME) more conducive to immunotherapy. We evaluated the gene signature of human tumors treated with the anti-EGFR agent, panitumumab.

Methods: To compare the relative influence of anti-EGFR therapy we evaluated patients who had been infused with fluorescently-labeled panitumumab (pan800) so that we could identify high and low regions of drug within the tumor. Spatial RNA sequencing of cancer cells and stromal cells from FFPE tissue regions of 6 patients was performed. Patients with high pan800 tumor concentrations (n=3) and patients with low pan800 concentrations (n=3) were assessed by Nanostring GeoMx DSP platform. Multi-region sampling of RNA expression of pro-tumor cytokines (IL6, IL10, CCL2, TGF- β, VEGF-A) and anti-tumor cytokines (TNF-α, IFN- γ, IL2, IL12, IL15) were assessed.

Results: In low-drug areas (LDAs), there was significantly more of the pro-tumor cytokine IL6 (1172 TPM) relative to high-drug areas (HDAs) (407 TPM) (p=0.04). There was also significantly more CCL2 (745 TPM) in LDAs relative to HDAs (233 TPM) (p=0.008). Differences in other cytokines did not reach significance between the two groups.

Conclusions: There was a significantly lower expression of pro-tumor cytokines IL6 and CCL2 present in high compared to low-drug tumor samples. By reducing these pro-tumor cytokines, anti-EGFR therapy can promote an anti-tumor cytokine microenvironment that could potentiate immunotherapy.