William H. Tomaszewski

Dec 25, 2024 | cell.com | Jessica Waibl Polania |Alexandra M Hoyt-Miggelbrink |William H. Tomaszewski |Lucas P Wachsmuth |Selena J. Lorrey |Daniel Wilkinson | +5 more

Keywords T cell exhaustion tumor-associated macrophage tumor microenvironment tumor immunology immunotherapy brain tumor brain metastasis glioblastoma Introduction Brain tumors, both primary and metastatic, continue to herald poor survival.1,2 Immunotherapies, such as immune checkpoint blockade (ICB) and chimeric antigen receptor (CAR) T cells, hold promise for improving outcomes but remain only marginally effective within the intracranial confines.3,4 This has been especially true in the...

Nov 25, 2024 | biorxiv.org | Jessica Waibl Polania |Alexandra M Hoyt-Miggelbrink |William H. Tomaszewski |Lucas P Wachsmuth

AbstractWhereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor exhausted T (Tex_prog) cells better reflect immunotherapeutic responsivity. Here, we examined the intratumoral cellular interactions that govern the transition to terminal T cell exhaustion. We defined a metric reflecting the intratumoral progenitor exhaustion-to-terminal exhaustion ratio (PETER), which decreased with tumor progression in solid cancers.

Aug 14, 2023 | biorxiv.org | William H. Tomaszewski |Jessica Waibl Polania |Alexandra M Hoyt-Miggelbrink |Lucas P Wachsmuth

AbstractWhile terminally exhausted T cells (Tex_term) retain important anti-tumor cytotoxic function, it is the relative preservation of renewable, stem-like progenitor exhaustion (Tex_prog) that better indicates immunotherapeutic responsivity. Although restraining the progression from Tex_prog to Tex_term thus takes on clinical significance, the cellular interactions in a tumor microenvironment (TME) governing such progression remain less established.