AUTHOR=Xia Chao , Huang Wei , Chen Yun-Liang , Fu Hai-Bin , Tang Ming , Zhang Tao-Lan , Li Jing , Lv Guo-Hua , Yan Yi-Guo , Ouyang Zhi-Hua , Yao Nvzhao , Wang Cheng , Zou Ming-Xiang 

TITLE=Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.797407

DOI=10.3389/fimmu.2021.797407

ISSN=1664-3224

ABSTRACT=Background: Immunotherapy only achieves efficacy in some cancer patients, and less is known about other immune checkpoint molecules in chordoma. Here, we aimed to determine the expression of PD-L1, HHLA2, B7H3, IDO-1 and Galectin-9 in spinal chordoma and evaluated their association with tumor infiltrating lymphocytes (TILs), clinicopathological characteristics and survival of patients.
Methods: Using multiplexed quantitative immunofluorescence (QIF), we simultaneously measured the levels of five different immune checkpoint molecules and major TIL subsets in 92 human spinal chordoma samples.
Results: Tumor HHLA2 and PD-L1 were positive in 80.0% and 86.0% of cases, respectively. However, B7H3, IDO-1 and Galectin-9 positivity on tumor cells were only seen in 21.0% of cases, despite all showing predominantly stromal expression. Coexpression of these QIF markers in the tumor compartment was scarcely detected except for PD-L1 and HHLA2, which was observed in 69.6% of cases. While tumoral HHLA2 and stromal B7H3 expressions were associated with an aggressive tumor phenotype, suppressive immune response (specifically including elevated PD+ TILs level and decreased CD8+ TIL density) and poor prognosis, stromal levels of PD-L1 and Galectin-9 predicted the opposite outcomes. Importantly, HHLA2 and PD-L1 coexpression on tumor cells independently predicted both worse local recurrence-free survival and overall survival.
Conclusion: These data provide a better understanding of the immunosuppressive mechanism in chordoma and may be useful for the development of combination or novel immunotherapy approaches aiming to improve therapeutic efficacy and survival.