Fairwind said...
Once again, the mice are rejoicing..
No, they are not. Imagine being a (healthy) mouse and getting cancer introduced in your tiny body by some human giants in lab coats...
More seriously, unlike many press announcements, this appears to be an important contribution that might explain why solid cancers appear to be more resistant to immunotherapical approaches. If correct, this may lead to new therapies.
Here is a link to the paper in Cell:
https://www.ncbi.nlm.nih.gov/pubmed/31730856and here is the Summary:
Immune checkpoint therapy (ICT) shows encouraging results in a subset of patients with metastatic castration-resistant prostate cancer (mCRPC) but still elicits a sub-optimal response among those with bone metastases. Analysis of patients’ bone marrow samples revealed increased T h17 instead of T h1 subsets after ICT. To further evaluate the different tumor microenvironments, we injected mice with prostate tumor cells either subcutaneously or intraosseously. ICT in the subcutaneous CRPC model significantly increases intra-tumoral T h1 subsets and improves survival. However, ICT fails to elicit an anti-tumor response in the bone CRPC model despite an increase in the intra-tumoral CD4 T cells, which are polarized to T h17 rather than T h1 lineage. Mechanistically, tumors in the bone promote osteoclast-mediated bone resorption that releases TGF-β, which restrains T h1 lineage development. Blocking TGF-β along with ICT increases T h1 subsets and promotes clonal expansion of CD8 T cells and subsequent regression of bone CRPC and improves survival. Post Edited (Sr Sailor) : 11/29/2019 9:43:12 AM (GMT-7)