AUG 07, 2017 6:34 PM PDT

Scanning Cancer's Genome to Uncover Resistance Genes

WRITTEN BY: Kara Marker

Cancer can't hide from the immune system anymore - scientists are on the verge of identifying every single gene mutation that enables tumors to resist the anti-cancer immune cell attack.

Dr. Neville Sanjana and a lab team member. Credit: New York Genome Center

Using a new application of the lauded CRISPR-CAS9 gene editing system, a team of scientists from the New York Genome Center, New York University, the Broad Institute, and the National Cancer Institute conducted a scan of the entire genome of the human melanoma tumor. The new gene editing technique is called two-cell type CRISPR assay system (2CT CRISPR).

“We cast a wide, deep net and conducted an unbiased survey of all of the 19,000 genes in the cancer's genome - not just the genes that are known to be involved in creating immunotherapy-resistant tumors," explained senior author Dr. Nicholas P. Restifo from the National Cancer Institute.

2CT-CRISPR is designed to flesh out the details of how the genetic alterations found in one cell impact how two different cell types communicate, using human T cells and human melanoma tumor cells. T cells are often the main ingredient in immunotherapy drugs because of their natural affinity for targeting cancerous cells. For this particular study, Restifo and the other researchers wanted to know: How are tumors avoiding the power of immunotherapy?

The new system allowed the each of the 19,000 tumor genes to be knocked out and tested for resistance - one at a time. This way, researchers could clearly associate a particular gene mutation with increased tumor resistance. At the end of the scan, the system identified many genes involved in helping tumors resist immunotherapy, including genes that scientists hadn’t realized were involved in tumor defense at all.

The study scientists then compared their findings to genes from the Cancer Genome Atlas, which contains genes spanning thousands of tumor and cancer types. In addition to finding gene mutations specific to melanoma’s resistance to immunotherapy, the comparison strengthened the idea that there is a “core set” of genes that are required for the immune system to successfully target any type of cancer.

“The top two hits - HLA and B2M - form a complex that is required for antigen presentation and thus required for the T cells to see and attack the cancer,” explained co-first author Dr. Neville anjana from the New York Genome Center. “Seeing these genes at the top of the list is a really nice sign that the genetic screen yielded meaningful data.”

Future studies building on the current findings could include other types of immune cells, using 2CT-CRISPR to see how different cell types work in different environments of gene mutations.

"This is the first step for systematically identifying the reasons immunotherapy is not working for many cancer patients," Restifo said. "The hope is to help scientists and clinicians find a way around the obstacles so that more patients can benefit from this promising treatment modality."

The present study was published in the journal Nature.

Source: New York Genome Center

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
MAR 04, 2021
Immunology
Why Do We Need Two Shots of the COVID Vaccine?
MAR 04, 2021
Why Do We Need Two Shots of the COVID Vaccine?
Unlike social distancing, mask-wearing, and hand hygiene, vaccines are our best bet as a long-term solution to protectin ...
APR 15, 2021
Immunology
COVID Vaccines Protect Breastfeeding Babies Too
APR 15, 2021
COVID Vaccines Protect Breastfeeding Babies Too
Good news for families of newborns: A new study shows that breastfeeding mothers who receive a COVID vaccine share prote ...
APR 21, 2021
Immunology
Human T Cells Can't Recognize COVID Mutants
APR 21, 2021
Human T Cells Can't Recognize COVID Mutants
Genetic variants of the SARS-CoV-2 virus have emerged and tightened their grip on global communities as the pandemic rag ...
MAY 10, 2021
Coronavirus
Researchers Create a Vaccine For Multiple SARS Viruses, Including COVID-19 & Variants
MAY 10, 2021
Researchers Create a Vaccine For Multiple SARS Viruses, Including COVID-19 & Variants
The pandemic virus SARS-CoV-2 has changed the world in devastating ways, taking hundreds of thousands of lives & new var ...
MAY 19, 2021
Drug Discovery & Development
Combination Immunotherapy Shows Promise in Treating HIV
MAY 19, 2021
Combination Immunotherapy Shows Promise in Treating HIV
  Researchers have found that a new combination immunotherapy, alongside antiretroviral therapy (ART), is effective ...
JUN 17, 2021
Immunology
How T Cells Sense Dangerous Invaders
JUN 17, 2021
How T Cells Sense Dangerous Invaders
T cells form a major part of our immune defenses, protecting us against the constant barrage of potentially pathogenic p ...
Loading Comments...