The physical size of the structural aspect of pancreatic adenocarcinoma
can be misleading as perhaps 90% of the tumor bulk is actually the
somewhat inert – and not completely understood – stromal tissue that the
“surrounds” the malignant aspect of pancreatic cancer. One practical
effect of the stromal tissue is that it may physically, through
mediating immunosuppression, and otherwise tend to block the effects of
standard treatment modalities – including immunotherapy.
Researcher Fearon and colleagues from Cambridge University UK recently
published findings in the December 10, 2013 issue of the Proceedings of
the National Academy of Sciences of the United States of America
detailing their work in attempting to account for and defeat the effects
of the tumor-protective stromal tissue utilizing a mouse model in the
experimental treatment of pancreatic cancer.
The authors employed the immune-stimulant drug-agent plerixafor (also
known as AMD3100) that is in use in the U.S. for such matters as stem
cell transplantation, and the treatment of AIDS (past usage), lymphoma
and multiple myeloma. Typically, the combination of G-CSF and plerixafor
increases stem cell mobilization in peripheral blood. Also, as another
aspect of its mechanisms of action, plerixafor in the immune system is a
partial antagonist of ligand 12 of the alpha chemokine receptor CXCR4
that depletes the stroma-supporting carcinoma-associated fibroblasts
that express fibroblast activation protein.
On administering plerixafor – the researchers were able to determine
that the agent greatly diminished the mouse pancreatic cancer cells and
rapidly increased local T-cell accumulation. Further and importantly,
the authors through this study have given credence to the gate-keeper
aspect that carcinoma-associated fibroblasts may be exerting through
stroma – that tends to defeat standard therapy in pancreatic cancer (and
other adenocarcinomas). By teasing out the mechanism of this process,
the authors are moving us closer to improved treatment options for
This is highly interesting early work that is deserving of
confirmation and more complete explication.
Dale O’Brien, MD