Carbon Black Deposition in Regional Lymph Nodes Is Associated with Disease Control after Immune Checkpoint Inhibitor-Based Therapy in Recurrent Esophageal Squamous Cell Carcinoma.

Abstract

Carbon black (CB) deposition, or anthracosis, is frequently observed in the regional lymph nodes (RLNs) of patients with thoracic malignancies, particularly those with a history of smoking; however, its clinical significance in immune checkpoint inhibitor (ICI)-based therapy remains unclear. This retrospective study aimed to investigate the association between CB deposition in RLNs and response to ICI-based therapy in recurrent esophageal squamous cell carcinoma (ESCC). The study included 47 patients with recurrent ESCC who underwent curative-intent esophagectomy and subsequently received ICI-based therapy. The proportion of CB-containing RLNs (%CB) was histologically evaluated, and patients were divided into high- and low-CB groups according to the median %CB value. CB was mainly detected in lymph node sinus macrophages. Patients in the high-CB group showed a significantly higher disease control rate than those in the low-CB group. Progression-free survival tended to be longer in the high-CB group, although the difference did not reach statistical significance. CB-containing sinus macrophages expressed CD68 and CD163, whereas CD169 expression was markedly reduced or absent. No significant association was observed between %CB and tumor-infiltrating immune cell densities or HLA class I/PD-L1 expression. By contrast, ectopic HLA-DR expression in cancer cells was more frequent in the high-CB group. These findings suggest that a higher proportion of CB-containing RLNs is associated with disease control following ICI-based therapy in recurrent ESCC. Histological assessment of CB deposition in RLNs may provide useful information regarding clinical benefit from ICI-based immunotherapy.