Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values

Kim, A. Reum; Choi, Kyu Sung; Kim, Min Sung; Kim, Kyung Min; Kang, Hee Yoon; Kim, Sojin; Chowdhury, Tamrin; Yu, Hyeon Jong; Lee, Chae Eun; Lee, Joo Ho; Lee, Sang Kun; Won, Jae Kyung; Kim, Jin Wook; Kim, Yong Hwy; Kim, Tae Min; Choi, Seung Hong; Shin, Eui Cheol; Park, Shin Young

doi:10.1007/s00262-020-02836-w

Cited by 27 publications

(21 citation statements)

References 39 publications

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“…Tumor-infiltrating immune cells were proved to be essential in the invasion progress of gliomas 37 . Therefore, it is necessary to explore the relationship between CTSB and infiltrating immune cells in gliomas.…”

Section: Resultsmentioning

confidence: 99%

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Chen

Liu

et al. 2022

Sci Rep

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Previous researches have demonstrated the meaning of CTSB for the progress of several tumors, whereas few clues about its immunological characteristic in gliomas. Here we systematically explored its biologic features and clinical significance for gliomas. 699 glioma cases of TCGA and 325 glioma cases of CGGA were respectively included as training and validating cohorts. R software was used for data analysis and mapping. We found that CTSB was remarkably highly-expressed for HGG, IDH wild type, 1p19q non-codeletion type, MGMT promoter unmethylation type and mesenchymal gliomas. CTSB could specifically and sensitively indicate mesenchymal glioma. Upregulated CTSB was an independent hazard correlated with poor survival. CTSB-related biological processes in gliomas chiefly concentrated on immunoreaction and inflammation response. Then we proved that CTSB positively related to most inflammatory metagenes except IgG, including HCK, LCK, MHC II, STAT1 and IFN. More importantly, the levels of glioma-infiltrating immune cells were positively associated with the expression of CTSB, especially for TAMs, MDSCs and Tregs. In conclusion, CTSB is closely related to the malignant pathological subtypes, worse prognosis, immune cells infiltration and immunosuppression of gliomas, which make it a promising biomarker and potential target in the diagnosis, treatment and prognostic assessment of gliomas.

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Section: Resultsmentioning

confidence: 99%

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Chen

Liu

et al. 2022

Sci Rep

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“…The percentage of each immune cell subset among the CD45 + cells was determined, and the number of cells in each immune cell subset was calculated as the cell number/gram of tumor tissue by multiplying the above values. 45 …”

Section: Methodsmentioning

confidence: 99%

Spatial immune heterogeneity of hypoxia-induced exhausted features in high-grade glioma

et al. 2022

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The tumor immune microenvironment (TIME) in high-grade glioma (HGG) exhibits high spatial heterogeneity. Though the tumor core and peripheral regions have different biological features, the cause of this spatial heterogeneity has not been clearly elucidated. Here, we examined the spatial heterogeneity of HGG using core and peripheral regions obtained separately from the patients with HGG. We analyzed infiltrating immune cells by flow cytometry from 34 patients with HGG and the transcriptomes by RNA-seq analysis from 18 patients with HGG. Peripheral region-infiltrating immune cells were in vitro cultured in hypoxic conditions and their immunophenotypes analyzed. We analyzed whether the frequencies of exhausted CD8 + T cells and immunosuppressive cells in the core or peripheral regions are associated with the survival of patients with HGG. We found that terminally exhausted CD8 + T cells and immunosuppressive cells, including regulatory T (T REG ) cells and M2 tumor-associated macrophages (TAMs), are more enriched in the core regions than the peripheral regions. Terminally exhausted and immunosuppressive profiles in the core region significantly correlated with the hypoxia signature, which was enriched in the core region. Importantly, in vitro culture of peripheral region-infiltrating immune cells in hypoxic conditions resulted in an increase in terminally exhausted CD8 + T cells, CTLA-4 + T REG cells, and M2 TAMs. Finally, we found that a high frequency of PD-1 + CTLA-4 + CD8 + T cells in the core regions was significantly associated with decreased progression-free survival of patients with HGG. The hypoxic condition in the core region of HGG directly induces an immunosuppressive TIME, which is associated with patient survival.

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“…These numbers are lower than what has been reported historically 39 , 40 (reviewed in 34 , 35 ), but higher than a recent report. 41 The differences in overall numbers could be due to heterogeneity in the tumor or possibly due to population level variations. With respect to the number of neutrophils, Liang et al 26 have demonstrated that neutrophil infiltration of gliomas increases with the grade, and that these cells may be responsible for disease progression and therapy resistance.…”

Section: Methodsmentioning

confidence: 99%

Immuno-phenotyping of IDH-mutant grade 3 astrocytoma and IDH-wildtype glioblastoma reveals specific differences in cells of myeloid origin

et al. 2021

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Gliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade 3 and grade 4 or GBM) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high-grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, IDH-wild type) or grade 3 IDH-mutant gliomas. We observe that neutrophils are highly heterogeneous among individuals with glioma, and are different from healthy controls. We also show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade 3 IDH-mutant glioma tissue, and a larger proportion of granulocytic myeloid-derived suppressor cells are present in grade 3 IDH-mutant gliomas when compared to GBM. Finally, we demonstrate that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor and suggest that these may be used as possible markers for prognosis.

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Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values

Cited by 27 publications

References 39 publications

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

CTSB is a negative prognostic biomarker and therapeutic target associated with immune cells infiltration and immunosuppression in gliomas

Spatial immune heterogeneity of hypoxia-induced exhausted features in high-grade glioma

Immuno-phenotyping of IDH-mutant grade 3 astrocytoma and IDH-wildtype glioblastoma reveals specific differences in cells of myeloid origin

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