A crucial signaling pathway that can tell the immune system to fight off cancer can also be co-opted by cancer cells to put the brakes on the immune system, according to a new study from researchers. Researchers say this increased understanding can serve as a biomarker that helps predict which patients are likely to respond to immunotherapies. They also show how tipping the balance has potential implications for therapy itself, since blocking the signal in cancer cells helps the immune system fight off tumors in multiple pre-clinical cancer models. The study was published in Cell.
The study focused on the interferon (IFN) signaling pathway. Interferons normally help activate the immune system to protect cells from viruses and get their name because they literally interfere with a virus' ability to spread. However, IFNs can also put the brakes on the immune system.
"This paradoxical effect has been seen in other diseases - such as chronic viral infections - but our study shows how cancer cells take advantage of the suppressive properties of IFNs to interfere with cancer immunotherapy," said the study's senior author.
This study builds on previous research, which initially identified IFNs as having a role in cancer immunotherapy resistance. For the current study, researchers found when IFNs put a brake on the immune system, cancer cells intercept and manipulate that signal. However, when IFNs are allowed to send signals to the immune system, immune cells are able to do their jobs and kill tumors. Understanding this balance of how IFN signals are routed to immune versus cancer cells could provide a biomarker for whether immunotherapy can be effective.
"If we know the signaling is tilted toward immune cells or toward cancer, we may be able to better predict if a patient is likely to respond," the author said.
For cases where IFNs signal is stronger in cancer cells, there could be a therapeutic answer. Blocking the signal in tumors would only leave the "go" signal, freeing up the immune system to attack the cancer. That's exactly what happened when researchers tested the theory in pre-clinical models of melanoma, breast, and colorectal cancer treated with immunotherapies like PD-1 inhibitors or CAR T cells.
"IFN signaling exists in the majority of human cancers, so this could end up applying more broadly," the author said.
The next step is to figure out novel and safe ways to make IFNs' "go" signal stronger, or to block the "stop" signal. A trial testing that second approach in lung cancer patients is already enrolling patients.
https://www.pennmedicine.org/news/news-releases/2019/august/balance-of-stop-and-go-signaling-could-be-key-to-cancer-immunotherapy-response
https://www.cell.com/cell/fulltext/S0092-8674(19)30784-6
Modulating interferon signaling to control cancer immunotherapy response
- 1,759 views
- Added
Edited
Latest News
Complete vascularization of…
By newseditor
Posted 28 Mar
Immune cells identified as…
By newseditor
Posted 28 Mar
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Other Top Stories
Long-non coding RNAs promote breast cancer metastasis
Read more
How shattered chromosomes (chromothripsis) make cancer cells drug-r…
Read more
Phase 3 clinical trial reveals life saving drug for acute myeloid l…
Read more
Brain cancer linked to tissue healing
Read more
The hexosamine biosynthesis pathway is a targetable liability in KR…
Read more
Protocols
Spatial proteomics in neuro…
By newseditor
Posted 28 Mar
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Publications
A microfluidic platform int…
By newseditor
Posted 28 Mar
Salmonella manipulates macr…
By newseditor
Posted 28 Mar
BHLHE40/41 regulate microgl…
By newseditor
Posted 28 Mar
Balancing neuronal activity…
By newseditor
Posted 28 Mar
OSBP-mediated PI(4)P-choles…
By newseditor
Posted 28 Mar
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