Nav: Home

Early immune response may improve cancer immunotherapies

December 03, 2019

In a paper published in the Journal of Biological Chemistry, University of Illinois at Chicago researchers and colleagues report a new mechanism for detecting foreign material during early immune responses.

Viruses, bacteria and cancer have many ways to replicate and survive in our bodies. For viruses and bacteria, they invade a cell directly to avoid detection. Cancer cells have the advantage of being native in the body. However, the body has safeguards against such sneaky tactics.

"There are proteins in the cell that await the presence of foreign material," said Marlene Bouvier, senior author and UIC professor of microbiology and immunology at the College of Medicine. "One protein, called endoplasmic reticulum aminopeptidase 1, or ERAP1, is programmed to find foreign material, like viral and bacterial proteins, and break it into smaller parts, also known as peptides. Another protein -- major histocompatibility complex class I, or MHC I -- is programmed to attach itself to a foreign peptide and move it to the cell's surface. With the foreign peptide outside the cell, immune cells can recognize and destroy the infected cell."

This is an example of a normal process, Bouvier said, but sometimes a foreign peptide, once bound to MHC I, remains in the cell. This happens when the foreign material is not broken down to a small enough size or is too long.

Bouvier and colleagues used X-ray crystallography -- a method to see structures on an atomic level -- and mass spectrometry -- used to identify peptide length by mass -- to show that ERAP1 can cut extra-long peptides even after they have bound to MHC I.

"X-ray crystallography allowed us to determine three-dimensional structures to see how these longer peptides bound to the MHC I groove with high resolution," Bouvier said. "Using an ERAP1 enzymatic assay with mass spectrometry gave us the ability to show, for the first time, that ERAP1 can trim peptides bound to MHC I. These tools allowed us to develop a model of this new immune response mechanism."

Bouvier said this new information may help researchers leverage ERAP1 to fight infections and cancer.

"This research can have major implications for immunotherapies," said Bouvier. "For example, cancer cells do not always present enough peptides to be labeled as 'foreign' -- allowing the cancer cells to replicate and grow. But if you have a way to manipulate how ERAP1 generates cancer peptides, then you can hopefully skew the peptide repertoire that is presented on the cell surface in our favor. This is the most translational application of our research."

This study was selected as the journal's "Editors' Pick" for the significance and importance of their research to the immunology field.
-end-
Lenong Li and Mansoor Batliwala from the department of microbiology and immunology in the UIC College of Medicine are co-authors on the paper.

This work was funded by the U.S. National Institute of Allergy and Infectious Diseases (AI114467, AI108546).

University of Illinois at Chicago

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.