Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
| Autor: | Nong Lin, Dan Zhu, Xiaobo Yan, Guo-Qi Li, Yanbiao Fu, Xiaoya Li, Peng Lin, Mark C. Poznansky, Patrick P. Lin, Zenan Wang, Huabiao Chen, Jiangnan Zhang, Zhaoming Ye, Binghao Li, Xiuliang Zhu, Hui Dai, Xuexin He, Hao Qu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Chemokine biology medicine.diagnostic_test business.industry Myeloid-Derived Suppressor Cells medicine.medical_treatment Chondrosarcoma Immunotherapy Malignancy medicine.disease Phenotype Flow cytometry Immune system Oncology Tumor Microenvironment biology.protein medicine Cancer research Humans Biomarker (medicine) Antibody business Retrospective Studies |
| Zdroj: | Clinical Cancer Research. 27:6543-6558 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-21-1893 |
| Popis: | Purpose: There is still no standard nonsurgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any CHSs have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor. Experimental Design: We obtained 98 newly-diagnosed CHS fresh tumors from several institutions and performed comprehensive analysis of data from CyTOF, whole-exome sequencing, and flow cytometry in 22 cases. Clinical data from immunotherapy responders and nonresponders were compared to explore possible biomarkers of immunotherapy response. Mechanism studies were conducted to interpret the biomarker phenotype. Results: Based on the integrated data of single-cell CyTOF and flow cytometry, the CHS immune-microenvironment phenotypes were classified into three groups: subtype I, the “granulocytic–myeloid-derived suppressor cell (G-MDSC) dominant” cluster, with high number of HLA-DR− CD14− myeloid cells; subtype II, the “immune exhausted” cluster, with high exhausted T-cell and dendritic-cell infiltration; and subtype III, the “immune desert” cluster, with few immune cells. Immune cell–rich subtypes (subtype I and II) were characterized by IDH mutation, pathologic high grade, and peritumoral edema, while subtype I cases were exclusively featured by myxoid transformation. In clinical practice involving 12 individuals who received PD-1 antibody immunotherapy, all of the 3 cases with controlled diseases were retrospectively classified as subtype II. In mechanism, IDH mutation significantly elevated chemokine levels and immune-cell infiltration in immune-inactivated tumors. Conclusions: This study is the first to provide immune characterization of CHS, representing a major step to precise immunotherapy against this malignancy. Immunotherapy is promising for the “immune exhausted” subtype of patients with CHS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|