Tumor-secreted lactate contributes to an immunosuppressive microenvironment and affects CD8 T-cell infiltration in glioblastoma

Abstract

Introduction: Glioblastoma is a malignant brain tumor with poor prognosis. Lactate is the main product of tumor cells, and its secretion may relate to immunocytes' activation. However, its role in glioblastoma is poorly understood.

Methods: This work performed bulk RNA-seq analysis and single cell RNA-seq analysis to explore the role of lactate in glioblastoma progression. Over 1400 glioblastoma samples were grouped into different clusters according to their expression and the results were validated with our own data, the xiangya cohort. Immunocytes infiltration analysis, immunogram and the map of immune checkpoint genes' expression were applied to analyze the potential connection between the lactate level with tumor immune microenvironment. Furthermore, machine learning algorithms and cell-cell interaction algorithm were introduced to reveal the connection of tumor cells with immunocytes. By co-culturing CD8 T cells with tumor cells, and performing immunohistochemistry on Xiangya cohort samples further validated results from previous analysis.

Discussion: In this work, lactate is proved that contributes to glioblastoma immune suppressive microenvironment. High level of lactate in tumor microenvironment can affect CD8 T cells' migration and infiltration ratio in glioblastoma. To step further, potential compounds that targets to samples from different groups were also predicted for future exploration.

Keywords: CD8+ T cells; chemotherapy; glioblastoma; immunocytes; interferon-gamma.