Insulin-Like Growth Factor 1 Receptor Expression for Predicting PD‑1/PD‑L1 Inhibitor Response in Hypopharyngeal Squamous Cell Carcinoma

Abstract

Objectives: Insulin-like growth factor 1 receptor (IGF-1R) is crucial for immunological control and the development of different types of cancer. It is still uncertain how the expression of IGF-1R impacts hypopharyngeal squamous cell carcinoma (HPSCC) and whether it has any predictive value for prognosis. Therefore, this study aimed to investigate the prognostic value of IGF-1R in HPSCC and its connection to tumor immunity.

Methods: Correlation between IGF-1R, p16, and tumor-infiltrating immune cells from the TCGA HNSCC data set was analyzed. The expressions of IGF-1R and programmed death ligand (PD-L1) and immune cell density were analyzed using immunohistochemistry (IHC) and multiplex immunohistochemistry (mIHC) in p16+/p16- HPSCC. Overall, 114 surgical specimens from 51 p16+ patients and 63 p16- patients with a bioptic diagnosis of HPSCC who underwent surgical resection at the Second Affiliated Hospital of Harbin Medical University were analyzed.

Results: IGF-1R and PD-L1 were expressed in tumor cells and invasion-front immune cells. Expression of IGF-1R and PD-L1 was related to tumor grade and lymph node status. In patients with p16- HPSCC, IGF-1R and PD-L1 expression were significantly higher than those with p16+ HPSCC, as were CD68+ or CD163+ cell densities. PD-L1 expression and CD68+ macrophage density were positively correlated with IGF-1R expression in p16+ HSPCC. In the p16+ HPSCC group, the co-expression rate of IGF-1R/PD-L1 was significantly increased.

Conclusion: IGF-1R expression could potentially serve as a better predictor of PD-1/PD-L1 inhibitor response rate in patients with HPSCC compared to p16 status. Combination therapy using IGF-1R inhibitors and PD-1/PD-L1 blockade may prove to be an effective treatment approach for patients with p16+ HPSCC.

Keywords: IGF‐1R; PD‐L1; hypopharyngeal neoplasms; immunotherapy; p16; squamous cell carcinoma.