PD-L1 expression and immune cells infiltration in primary tracheobronchial neoplasm

Background: Primary tracheobronchial neoplasm is rare yet poses a serious threat to life. Due to its low incidence, the immune microenvironment of such tumors remained unclear. This study aimed to clarify the expression of programmed death-ligand 1 (PD-L1) and infiltration of immune cells in primary tracheobronchial neoplasm, which might be useful for guiding treatment and evaluating clinical outcome.

Methods: We assessed retrospectively the expression of PD-L1 and infiltration in cells expressing CD8, CD16, CD68, CD163 and FOXP3 in 21 patients with primary tracheobronchial neoplasm who underwent surgery in Tangdu Hospital from January 2016 to July 2021. The expression of PD-L1 was assessed based on the tumor proportion score system. The density of immune cells was analyzed by automatic image analysis software.

Results: In this study, all of 16 participants with adenoid cystic carcinoma (ACC) had no expression of PD-L1, whereas 4/5 (80%) of those with squamous cell carcinomas (SCC) were positive for PD-L1 expression. Compared with ACC, the density of FOXP3⁺ cells in both the intratumoral region and peritumoral region was higher in SCC (P<0.01). The density of FOXP3⁺ cells was significantly higher than that of CD8⁺, CD16⁺, and CD163⁺ cells in SCC in the intratumoral region (P<0.01). In contrast, the density of FOXP3⁺ cells was significantly lower than that of CD8⁺, CD16⁺, and CD68⁺ cells in ACC in both the intratumoral region and peritumoral regions. The density of CD68⁺ cells was significantly higher than that of CD8⁺ cells (P<0.05) and CD163⁺ cells (P<0.01) in ACC in the intratumoral region. Furthermore, the tumors of patients with metastasis more commonly of immune-excluded status, in which the CD8⁺ cells accumulated in peritumoral region.

Conclusions: This study demonstrated that the expression of PD-L1 in primary tracheobronchial neoplasm was mainly concentrated in patients with SCC. In the immune microenvironment of SCC, FOXP3⁺ cells were the dominant immune cells, while in the immune microenvironment of ACC, CD68⁺ cells were the main immune cells. Therefore, the immune microenvironment was significantly different in primary tracheobronchial neoplasm according to histology.