Saurabh Zanwar, Assistant Professor at Mayo Clinic, shared on X:
“Out now in Blood Cancer Journal.
Why does extramedullary myeloma (EMD) continue to have suboptimal responses to immune effector therapies?
Using imaging mass cytometry, we mapped >100,000 cells from EMD and solitary plasmacytoma (SPM).
The key finding: EMD TME shows marked heterogeneity characterised by immune exhaustion + spatial immune exclusion + regulatory niches.
Title: Spatial profiling of extramedullary multiple myeloma demonstrates immune-excluded and suppressive tumor microenvironment
Authors: Maximilian J. Steinhardt, Will Sherman, Mariam Stein, Yi Lin, Taxiarchis Kourelis, Dragan Jevremovic, Angela Dispenzieri, Morie A. Gertz, Karen L. Rech, Surendra Dasari, Jansen Seheult, Kevin Pavelko, Michael Strausbauch, Megan Weivoda, Wilson I. Gonsalves, Prashant Kapoor, S. Vincent Rajkumar, Shaji Kumar, Saurabh Zanwar
First, the T cells in EMD look different.
Helper T cells showed higher TIGIT, PD-1, PD-L1 and TIM-3 expression vs SPM.
Cytotoxic T cells also had higher TIGIT, PD-1 and PD-L1.
A checkpoint-rich, exhausted/suppressive phenotype.
But the spatial findings were perhaps more striking.
Compared with SPM, cytotoxic T cells in EMD were farther from:
- Plasma cells: 54.1 vs 31.2 μm
- Helper T cells: 50.8 vs 28.5 μm
- Dendritic cells: 37.7 vs 19.1 μm
Effector cells are spatially decoupled from tumor + antigen presentation.
And EMD wasn’t simply an immune desert.
Cytotoxic T cells preferentially localized near regulatory CD4+ populations, while malignant plasma cells had limited proximity to effector immune populations.
Organized immune suppression rather than simply absent immunity.
Our model: The immune cells may be there, but are poorly positioned to mount effective tumor control. This is small, hypothesis-generating study, and more work to follow Maximilian Steinhardt for getting it over the finish line.
Other articles about extramedullary myeloma on OncoDaily.