Pembrolizumab alters the tumor immune landscape in a patient with dMMR glioblastoma

Congenital DNA mismatch repair defects (dMMR), such as Lynch Syndrome, predispose patients to a variety of cancers and account for approximately 1% of glioblastoma cases. While few therapeutic options exist for glioblastoma, checkpoint blockade therapy has proven effective in dMMR tumors. Here we present a case study of a male in his 30s diagnosed with dMMR glioblastoma treated with pembrolizumab who experienced a partial response to therapy. Using a multiplex IHC analysis pipeline on archived slide specimens taken upon tumor resection at diagnosis and after therapeutic intervention, we quantified changes in the frequency and spatial distribution of key immune and tumor cell populations in the tissue. Notably, proliferating KI67+ macrophages and T cells increased in frequency as did KI67+ tumor cells. Therapeutic intervention remodeled the cellular spatial distribution in the tumor leading to a greater frequency of macrophage/tumor cell interactions and T cell/T cell interactions, highlighting the impact of checkpoint blockade on tumor cytoarchitecture and revealing spatial patterns indicative of advantageous immune interactions in glioma and other solid tumors treated with these agents.

This dataset includes serial multiplex IHC staining with CD3, CD8, CD4, IBA1, CD68, PD-1, PD-L1, KI67, hematoxylin (HEMA), and H&E (HNE) performed on 3 difference tumor tissue samples taken from a patient with Lynch Syndrome Associated glioblastoma.

N20-11-2E = 1st Resection

S21-030818-B1-6 = 2nd Resection

S21-15696-A1(35) = 3rd Resection