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

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.