Researchers have identified an unexpected mechanism that could help determine whether a cancer patient will respond to immunotherapy.
Ideally, the immune system identifies tumors as threatening elements and deploys immune cells (T cells) to find and kill them. However, tumor cells have evolved to employ a protein called PD-L1 to blind T cells from carrying out their functions and evade immune defenses. PD-L1 protects tumor cells by activating a "molecular brake" known as PD-1 to stop T cells.
In important therapeutic progress, antibodies developed to block PD-L1/PD-1 have been clinically proven to benefit certain cancer patients. Yet why some patients don't respond to such therapy has remained a mystery. Now, the researchers have uncovered some clues.
As described in the journal Cell Reports, the researchers discovered an unexpected twist in the tumor versus T cell battle. Some tumor cells display not only their PD-L1 weapon, but also the PD-1 "brake." This simultaneous expression leads PD-1 to bind and neutralize PD-L1 on the same tumor cell. Thus, the PD-L1 on these tumor cells can no longer engage the PD-1 brake on T cells.
"It's a very exciting finding," said the author. "Our study uncovered an unexpected role of PD-1 and another dimension of PD-1 regulation with important therapeutic implications."
This study suggests that patients with high levels of PD-1 on tumor cells may not respond well to the blocking antibodies because the PD-1 pathway is self-canceled. In these patients, mechanisms other than PD-L1/PD-1 are likely employed by the tumors to escape from immune destruction.
Looking to extend the immunotherapy potential of the finding, the researchers are now seeking to determine additional mechanisms of "self-cancellation" at the interface of the tumor and immune cells.
"We think that our finding is the tip of the iceberg," said the author. "We speculate that self-cancellation is a general mechanism to regulate immune cell function. Understanding these processes more clearly will help develop better immunotherapy strategies and more reliably predict whether a patient will respond or not."
https://ucsdnews.ucsd.edu/pressrelease/uc_san_diego_biologists_discover_process_that_neutralizes_tumors
https://www.cell.com/cell-reports/fulltext/S2211-1247(18)30964-1
Immune mechanism to neutralize tumors
- 3,045 views
- Added
Edited
Latest News
Circadian rhythms can influ…
By newseditor
Posted 27 Apr
With hybrid brains, these m…
By newseditor
Posted 27 Apr
Blocking activation of NF-κ…
By newseditor
Posted 27 Apr
Vitamin D regulates microbi…
By newseditor
Posted 27 Apr
Role of alternative splicin…
By newseditor
Posted 27 Apr
Other Top Stories
New information about bacterial enzymes to help scientists develop…
Read more
Mechanism of recruitment of human telomerase to telomeres
Read more
High-resolution imaging illuminates DNA repair
Read more
Oxygen Sensing by Arterial Chemoreceptors Depends on Mitochondrial…
Read more
Sensory illusion causes cells to self-destruct
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Single dose creatine improv…
By newseditor
Posted 27 Apr
Autonomous circadian rhythm…
By newseditor
Posted 27 Apr
Functional sensory circuits…
By newseditor
Posted 27 Apr
Positive selection CRISPR s…
By newseditor
Posted 27 Apr
Focal clusters of peri-syna…
By newseditor
Posted 27 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar