Uptake of positron emission tomography tracers reflects the tumor immune status in esophageal squamous cell carcinoma

Abstract

The relationship between the local immune status and cancer metabolism regarding ¹⁸ F-FDG and ¹⁸ F-FAMT uptake in esophageal squamous cell carcinoma (ESCC) remains unknown. The present study examined the correlations between tumor immune status, clinicopathological factors, and positron emission tomography (PET) tracer uptake in ESCC. Forty-one ESCC patients who underwent ¹⁸ F-FDG PET and ¹⁸ F-FAMT PET before surgery were enrolled in the study. Immunohistochemistry was conducted for programmed death 1 (PD-1), CD8, Ki-67, CD34, GLUT1 (¹⁸ F-FDG transporter) and LAT1 (¹⁸ F-FAMT transporter). ESCC specimens with high tumoral PD-L1 and high CD8-positive lymphocytes were considered to have "hot tumor immune status." High PD-L1 expression (53.7%) was significantly associated with tumor/lymphatic/venous invasion (P = 0.028, 0.032 and 0.018), stage (P = 0.041), CD8-positive lymphocytes (P < 0.001), GLUT1 (P < 0.001), LAT1 expression (P = 0.006), Ki-67 labelling index (P = 0.009) and CD34-positive vessel counts (P < 0.001). SUVmax of ¹⁸ F-FDG was significantly higher in high PD-L1 cases than in low PD-L1 cases (P = 0.009). SUVmax of ¹⁸ F-FAMT was significantly higher in high PD-L1 (P < 0.001), high CD8 (P = 0.012) and hot tumor groups (P = 0.028) than in other groups. High SUVmax of ¹⁸ F-FAMT (≥4.15) was identified as the only predictor of hot tumor immune status. High PET tracer uptake was significantly associated with cancer aggressiveness and hot tumor immune status in ESCC. PET imaging may be an effective tool to predict tumor immune status in ESCC with respect to immune checkpoint inhibitor sensitivity.

Keywords: CD8; FAMT-PET; FDG-PET; PD-L1; esophageal cancer; hot tumor.

Figure 1

Representative immunohistochemical staining and positron emission tomography (PET) imaging of patients with esophageal squamous cell carcinoma (ESCC). Representative immunostaining for programmed death ligand‐1 (PD‐L1) (A, original magnification 200×) and CD8 (B, original magnification 100×) expression in slides containing both ESCC and normal tissue (scale bar = 100 μm). PET imaging of ¹⁸F‐FDG (C) and ¹⁸F‐FAMT (D) in the same patient is shown

Figure 2

Overall survival of the study population according to programmed death ligand‐1 (PD‐L1) expression, CD8 expression and hot tumor immune status. A, Overall survival of esophageal squamous cell carcinoma (ESCC) patients according to tumoral PD‐L1 expression. B, Overall survival of ESCC patients according to infiltrating CD8‐positive lymphocytes. C, Overall survival of ESCC patients according to hot tumor immune status defined as high tumoral PD‐L1 expression and high infiltrating CD8‐positive lymphocytes in ESCC tissues. ESCC patient groups with high PD‐L1, high CD8 or hot tumor immune status were not associated with poor prognosis compared to the other groups

Figure 3

Relationship between positron emission tomography (PET) tracer uptake and programmed death ligand‐1 (PD‐L1), CD8 and hot tumor immune status in esophageal squamous cell carcinoma tissues. A, Correlation between SUVmax of ¹⁸F‐FDG and PD‐L1, CD8 and hot tumor immune status. SUVmax of ¹⁸F‐FDG in high PD‐L1 cases was significantly higher than that in low PD‐L1 cases (P = 0.009). B, Correlation between SUVmax of ¹⁸F‐FAMT and PD‐L1, CD8 and hot tumor immune status. The SUVmax of ¹⁸F‐FAMT in the high PD‐L1, high CD8 and hot tumor groups was significantly higher than that in the other groups (P < 0.001, P = 0.012 and P = 0.028, respectively)

Figure 4

Receiver operating characteristic (ROC) curve analyses for the optimal cut‐off value of positron emission tomography (PET) tracer uptake. ROC analyses for the potential of SUVmax for ¹⁸F‐FDG (A) and ¹⁸F‐FAMT (B) to discriminate between hot tumor immune status and others. The areas under the curve for hot tumor immune status were 0.654 and 0.701 for SUVmax of ¹⁸F‐FDG and ¹⁸F‐FAMT, respectively