Immunogenic mutations in tumor genomes correlate with increased patient survival

April 29, 2014

Developing immunotherapies for cancer is challenging because of significant variability among tumors and diversity in human immune types. In a study published online today in Genome Research, researchers examined the largest collection of tumor samples to date to predict patient-specific tumor mutations that may activate the patient's immune system, paving the way for more successful, personalized cancer immunotherapy.

Tumor cells accrue mutations in their DNA, and as these mutations accumulate, the cell looks less and less like part of the body and more like a foreign invader to the . Cancer with stronger anti-tumor immune responses, mediated by T cells, are more likely to live longer. Much research has focused on strategies to harness the immune system to fight ; however, it has been difficult to determine the tumor mutations that activate a patient's T cells because the mutations occur sporadically, and successful activation depends on the patient's immune type (specifically, their HLA type), which varies considerably from person to person.

In this new study, the authors used a collection of over 500 tumor samples to computationally predict, using both the mutation profile and the individual's immune type, which tumor mutations are likely to be "immunogenic," causing an immune response in the patient. They found that patients with one or more immunogenic mutations had higher expression of a known T cell marker, indicative of an anti-tumor T cell response. Furthermore, these patients had higher overall survival rates than patients without immunogenic mutations, suggesting the mutations are eliciting a protective .

This study highlights the "personalized nature of the tumor-immune interaction" said the lead author of the study, Robert Holt. "Cancer immunotherapy is most likely to be successful if it is personalized, that is, targeted to each individual patient's immune type and mutation profile." With the decreasing cost of DNA sequencing, "it is now feasible to map these mutational profiles and design individual vaccines in relatively short order," Holt said.

Furthermore, the study demonstrates that tumors harboring large numbers of mutations are more likely to benefit from , because they are more likely to have mutations that make the tumor susceptible to the immune system.

Holt added, "these results also support an entirely new approach to immunotherapy: creating personalized cancer vaccines that use tumor-specific immunogenic to enhance anti-tumor immunity." The team is now looking to apply this strategy in combination with conventional cancer therapies.

The data in this study was generated by The Cancer Genome Atlas (TCGA), a comprehensive resource of genomic information from a large number of patient samples, funded by the U.S. National Institutes of Health.

Explore further: Personalized treatment prolongs the life of lung cancer patients

More information: Brown SD, Warren RL, Gibb EA, Martin SD, Spinelli JJ, Nelson BH, Holt RA. 2014. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res doi: 10.1101/gr.165985.113

Related Stories

Personalized treatment prolongs the life of lung cancer patients

March 10, 2014
The National Cancer Institute (INCan) has progressed from a rate of nine months of survival to 30 with personalized treatments for patients diagnosed with lung cancer in metastatic stage, i.e., when the disease has spread ...

One cell type may quash tumor vaccines

April 28, 2014
Most cancer vaccines have not lived up to their promise in clinical trials. The reason, many researchers suspect, is that the immune cells that would help the body destroy the tumor – even those reactions boosted by cancer ...

Novel cancer vaccine holds promise against ovarian cancer, mesothelioma

March 5, 2014
A novel approach to cancer immunotherapy – strategies designed to induce the immune system to attack cancer cells – may provide a new and cost-effective weapon against some of the most deadly tumors, including ovarian ...

The immune system's redesigned role in fighting cancerous tumors

March 12, 2014
Researchers in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute eradicated solid tumors in laboratory mice using a novel combination of two targeted agents. These two synergistic therapies stimulate an immune ...

Cancer vaccine could use immune system to fight tumors

February 27, 2014
Cincinnati Cancer Center (CCC) and UC Cancer Institute researchers have found that a vaccine, targeting tumors that produce a certain protein and receptor responsible for communication between cells and the body's immune ...

Moffitt Cancer Center begins Phase I clinical trial of new immunotherapy

April 10, 2014
Moffitt Cancer Center has initiated a phase I clinical trial for a new immunotherapy drug, ID-G305, made by Immune Design. Immunotherapy is a treatment option that uses a person's own immune system to fight cancer. It has ...

Recommended for you

Large genetic study links tendency to undervalue future rewards with ADHD, obesity

December 11, 2017
Researchers at University of California San Diego School of Medicine have found a genetic signature for delay discounting—the tendency to undervalue future rewards—that overlaps with attention-deficit/hyperactivity disorder ...

Gene variants identified that may influence sexual orientation in men and boys

December 8, 2017
(Medical Xpress)—A large team of researchers from several institutions in the U.S. and one each from Australia and the U.K. has found two gene variants that appear to be more prevalent in gay men than straight men, adding ...

Disease caused by reduction of most abundant cellular protein identified

December 8, 2017
An international team of scientists and doctors has identified a new disease that results in low levels of a common protein found inside our cells.

Study finds genetic mutation causes 'vicious cycle' in most common form of amyotrophic lateral sclerosis

December 8, 2017
University of Michigan-led research brings scientists one step closer to understanding the development of neurodegenerative disorders such as ALS.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

Researchers find genes may 'snowball' obesity

December 7, 2017
There are nine genes that make you gain more weight if you already have a high body mass index, McMaster University researchers have found.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.