Complex immune microenvironment of chordoma: a road map for future treatment
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Published on: February 3, 2022
Hua-Qing Niu1, Bo-Yv Zheng2, Ming-Xiang Zou3
1Department of Ophthalmology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
Background:
Chordoma, a rare bone tumor, presents limited treatment options and patients typically exhibit poor survival outcomes. While immunotherapy has shown promising results in treating various tumors, research on the immune microenvironment of chordomas is still in its early stages. Therefore, understanding how the immune microenvironment of chordomas influences the outcomes of immunotherapy is crucial.
Methods:
We employed single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, CellChat, gene set variation analysis, as well as calculation of immune features to further dissect the complex immune microenvironment of chordoma.
Results:
Previous research by van Oost et al argued that compared with other sarcomas, chordomas typically exhibit an immunologically "hot" microenvironment, a conclusion with which we concur based on their research findings. Additionally, the authors suggest that T cell-mediated immunotherapy is feasible for the majority of chordomas. However, we are inclined to categorize them as an immune-excluded phenotype according to the latest classification methods, rather than persisting with the concepts of "cold" and "hot". Unlike them, we explored immune infiltration scores (IS), T lymphocyte scoring (TLS), and human leucocyte antigen class I (HLA-I) using Bulk RNA-seq data from 126 chordoma patients and found that higher IS, TLS, and higher HLA-I expression were associated with poorer patient prognosis. Additionally, CellChat analysis of scRNA-seq results from six chordoma patients revealed no direct interaction between T cells and tumor cells.
Conclusions:
These findings suggested that the efficacy of T cell-based immunotherapy may be limited or even ineffective for patients with chordoma.
Insights
Chordoma's immune microenvironment is immune-excluded, not "hot." Higher immune infiltration, T lymphocyte scores, and HLA-I expression correlate with poorer chordoma prognosis, suggesting limited T cell immunotherapy efficacy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Chordoma is a rare bone tumor with poor prognosis and limited treatment options.
- Understanding the tumor immune microenvironment is critical for developing effective chordoma therapies, particularly immunotherapy.
Purpose of the Study:
- To investigate the immune microenvironment of chordoma and its implications for T cell-mediated immunotherapy.
- To re-evaluate the immunological classification of chordoma based on current methodologies.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) were utilized.
- Analysis included CellChat, gene set variation analysis, and calculation of immune features like immune infiltration scores (IS), T lymphocyte scoring (TLS), and human leucocyte antigen class I (HLA-I) expression.
Main Results:
- Chordoma exhibits an immune-excluded phenotype, contrasting with a
- hot
- classification.
- Higher IS, TLS, and HLA-I expression in 126 chordoma patients were associated with poorer prognosis.
- scRNA-seq revealed no direct interaction between T cells and tumor cells in six patients.
Conclusions:
- The immune microenvironment of chordoma suggests limited efficacy for T cell-based immunotherapy.
- Chordoma patients may not benefit from current T cell immunotherapy strategies.
