15 research outputs found
The Sudbury Neutrino Observatory
The Sudbury Neutrino Observatory is a second generation water Cherenkov
detector designed to determine whether the currently observed solar neutrino
deficit is a result of neutrino oscillations. The detector is unique in its use
of D2O as a detection medium, permitting it to make a solar model-independent
test of the neutrino oscillation hypothesis by comparison of the charged- and
neutral-current interaction rates. In this paper the physical properties,
construction, and preliminary operation of the Sudbury Neutrino Observatory are
described. Data and predicted operating parameters are provided whenever
possible.Comment: 58 pages, 12 figures, submitted to Nucl. Inst. Meth. Uses elsart and
epsf style files. For additional information about SNO see
http://www.sno.phy.queensu.ca . This version has some new reference
Dendritic cell paucity in mismatch repair-proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy.
Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC