Tumor-infiltrating CD8+ sub-populations in primary and recurrent glioblastoma: An in-silico study

Abstract

Background: Glioblastoma multiforme (GBM) remains an incurable primary brain tumor. CD8⁺ tumor-infiltrating lymphocytes (TILs) can target malignant cells; however, their anti-tumoral immune responses mostly do not lead to GBM rejection in GBM patients. We profiled the sub-populations of tumor-infiltrating CD8⁺ T-cells, i.e., naïve, cytotoxic, and exhausted cells, in primary and recurrent GBM tissues and provided a blueprint for future precision-based GBM immunotherapy.

Method: We re-analyzed the raw data of single-cell RNA sequencing on the cells residing in the GBM microenvironment and leveraged tumor bulk RNA analyses to study the significance of CD8⁺ TILs sub-populations in primary and recurrent GBM. We investigated cell-cell interaction between exhausted CD8⁺ TILs and other immune cells residing in the primary and recurrent GBM microenvironments and profiled the expression changes following CD8⁺ TILs' transition from primary GBM to recurrent GBM.

Results: Exhausted CD8⁺ TILs are the majority of CD8⁺ TILs sub-populations in primary and recurrent GBM, and cytotoxic CD8⁺ TILs display decreased expression of inhibitory immune checkpoint (IC) molecules in the primary and recurrent GBM. In the primary and recurrent GBM microenvironment, exhausted CD8⁺ TILs interact most with tumor-infiltrating dendritic cells.

Conclusion: This study demonstrates the profiles of CD8⁺ TILs sub-populations in primary and recurrent GBM and provides a proof-of-concept for future precision-based GBM immunotherapy.

Keywords: CD8 lymphocytes; Glioblastoma; Immune checkpoint; Single-cell RNA sequencing.