ARHGDIB as a prognostic biomarker and modulator of the immunosuppressive microenvironment in glioma.

in Cancer immunology, immunotherapy : CII by Xuejun Yan, Rongnian Li, Jing Xu, Hua Liu, Minmin He, Xingjun Jiang, Caiping Ren, Quanwei Zhou

TLDR

  • The study identified ARHGDIB as a potential biomarker for poor glioma prognosis and found that it helps create an immunosuppressive microenvironment.
  • ARHGDIB is a key regulator of immune cell recruitment and polarization in glioma, making it a promising therapeutic target.

Abstract

Glioma, a prevalent malignant intracranial tumor, exhibits limited therapeutic efficacy due to its immunosuppressive microenvironment, leading to a poor prognosis for patients. ARHGDIB is implicated in the remodeling of the tumor microenvironment and plays a significant role in the pathogenesis of various tumors. However, its regulatory effect within the immune microenvironment of glioma remains unclear. The mRNA expression pattern of ARHGDIB was analyzed using public databases, and its expression was further validated in our collected cohort through quantitative PCR (qPCR) and immunohistochemistry (IHC). Kaplan-Meier survival analysis and LASSO-Cox regression were employed to ascertain the clinical significance of ARHGDIB in glioma. Subsequently, we systematically evaluated the association between ARHGDIB expression and immune characteristics within the glioma microenvironment, as well as its potential to predict treatment response in glioma. Additionally, in vitro experiments were conducted to elucidate the role of ARHGDIB in remodeling the glioma microenvironment and promoting tumor malignancy progression. Combined with bioinformatics analysis of public databases and validation with qPCR and IHC on our cohort, our findings indicate that ARHGDIB is markedly overexpressed in glioma and correlates with poor patient prognosis, thereby serving as a potential biomarker for adverse outcomes in glioma. Functional enrichment and immune infiltration analyses reveal that ARHGDIB is implicated in the recruitment of immunosuppressive cells, such as M2 macrophages and neutrophils, contributing to the alteration of the glioma immunosuppressive microenvironment and hindering the immune response. Further investigations through single-cell sequencing, immunohistochemistry, immunofluorescence, and in vitro experiments demonstrate that ARHGDIB exhibits an expression pattern akin to CD163, with its overexpression inducing M2 macrophage polarization and facilitating glioma cell proliferation and migration. ARHGDIB emerges as a novel marker for tumor-associated macrophages, playing a crucial role in shaping the immunosuppressive microenvironment and representing a promising prognostic biomarker for glioma.

Overview

  • The study aims to investigate the regulatory role of ARHGDIB in the immune microenvironment of glioma, a common brain tumor, and its potential as a biomarker for treatment response and patient prognosis.
  • The researchers analyzed public databases, validated ARHGDIB expression in a study cohort, and employed various methods, including Kaplan-Meier survival analysis and LASSO-Cox regression, to evaluate its clinical significance.
  • The study's primary objective is to determine the relationship between ARHGDIB expression and immune characteristics in glioma, including its potential to predict treatment response and patient prognosis.

Comparative Analysis & Findings

  • The study found that ARHGDIB is overexpressed in glioma and correlates with poor patient prognosis, making it a potential biomarker for adverse outcomes.
  • Functional enrichment and immune infiltration analyses revealed that ARHGDIB is involved in recruiting immunosuppressive cells, such as M2 macrophages and neutrophils, leading to a more suppressive microenvironment and hindering the immune response.
  • Single-cell sequencing, immunohistochemistry, immunofluorescence, and in vitro experiments confirmed ARHGDIB's role in inducing M2 macrophage polarization, promoting glioma cell proliferation and migration, and shaping the immunosuppressive microenvironment.

Implications and Future Directions

  • The study's findings suggest that ARHGDIB could be a promising biomarker for glioma prognosis and a potential therapeutic target to enhance immunotherapy efficacy.
  • Future research could investigate the mechanisms by which ARHGDIB regulates the immune microenvironment and its potential as a predictor of treatment response.
  • The identification of ARHGDIB as a marker for tumor-associated macrophages highlights the importance of macrophages in glioma progression and suggests that targeting macrophages may be an effective strategy for glioma treatment.
Read Full Article