High Expression of Tumor HLA-DR Predicts Better Prognosis and Response to Anti-PD-1 Therapy in Laryngeal Squamous Cell Carcinoma

Yu Heng; Xiaoke Zhu; Qian Wu; Hanqing Lin; Xuping Ding; Lei Tao; Liming Lu

doi:10.1016/j.tranon.2023.101678

High Expression of Tumor HLA-DR Predicts Better Prognosis and Response to Anti-PD-1 Therapy in Laryngeal Squamous Cell Carcinoma

Transl Oncol. 2023 Jul:33:101678. doi: 10.1016/j.tranon.2023.101678. Epub 2023 May 5.

Authors

Yu Heng¹, Xiaoke Zhu¹, Qian Wu², Hanqing Lin¹, Xuping Ding², Lei Tao³, Liming Lu⁴

Affiliations

¹ ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.
² Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
³ ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China. Electronic address: lei.tao@fdeent.org.
⁴ Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: youlanda2009@sjtu.edu.cn.

Abstract

Background: HLA-DR is expressed in epithelial and several types of tumor cells. However, the correlation between tumor-expressed HLA-DR (teHLA-DR) and patient outcome as well as its regulation on the tumor microenvironment (TME) of laryngeal squamous cell carcinoma (LSCC) are yet to be elucidated.

Methods: Hematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays. teHLA-DR tumor cell, CD4⁺ and CD8⁺ tumor-infiltrating T lymphocytes (TITLs) were obtained and analyzed through double-labeling immunofluorescence and immunohistochemical staining. The recurrence-free (RFS) and overall survival (OS) curves were plotted using the Kaplan-Meier method and tested by the log-rank test method. Expression of teHLA-DR⁺ tumor cells and infiltration of T lymphocytes and their corresponding subgroups were analyzed by flow cytometry using fresh LSCC tissue samples.

Results: Our research discovered elevated expressions of multiple MHC-II-related genes in tumor compared to the adjacent normal tissue samples of LSCC patients. We also found that patients in the teHLA-DR high-expression group (teHLA-DR^high) tend to have less tumor recurrence and better survival outcomes compared to those in the teHLA-DR^low group. Intriguingly, teHLA-DR⁺ tumor cells had significantly higher PD-L1 and PD-L2 expression and their TME showed increased infiltrated T lymphocytes (TITLs). Flow cytometry analysis and IHC staining indicated that CD4⁺ TITLs but not CD3⁺ total TITLs or CD8⁺ TITLs were significantly enriched in teHLA-DR⁺ tumors.

Conclusions: teHLA-DR may be a predictive marker for favorable prognosis and response to anti-PD-1/PD-L1 therapy of LSCC, possibly due to the increased CD4⁺ TITLs in the TME.

Keywords: Laryngeal squamous cell carcinoma; PD-L1; Personalized medicine; Tumor-expressed HLA-DR; Tumor-infiltrating T lymphocyte.