Researchers use new computational method to define immune cell interactions

March 15, 2017
Dartmouth researchers use new computational method to define immune cell interactions in the tumor microenvironment to quickly calculate the personal immune response profile for thousands of patients. Credit: Frederick S. Varn

Immunotherapy, harnessing a patient's immune system to help fight cancer, has shown much promise as a potential cancer treatment. In a newly published study, a research team at Dartmouth-Hitchcock's Norris Cotton Cancer Center (NCCC) illustrates that complex interactions between different immune cell types in the tumor microenvironment play meaningful roles in patient survival. The team used a new computational method to infer immune cell infiltration from patient gene expression data, enabling them to quickly calculate the personal immune response profile for thousands of patients. Their findings, Systematic Pan-Cancer Analysis Reveals Immune Cell Interactions in the Tumor Microenvironment will be published in the next issue of Cancer Research.

The study, which took place in the Chao Cheng laboratory at NCCC was led by Fred Varn, BS, a graduate student and PhD candidate in the Cheng laboratory. "In our publication, we were curious about how different affect each other in different cancer types. Some immune cells, such as CD8+ T cells, have -killing capabilities while others, such as T-regulatory cells and certain myeloid cells, can suppress these attacks. Understanding how these infiltrate different tumors and the effect these cells have on each other and the patient can help us understand how to better harness the power of the immune system for cancer therapy" said Varn.

The team used a computational method to outline the patterns of immune infiltration in different tumor types. They found that most immune cell types tend to co-infiltrate the tumor together, demonstrating the importance of accounting for the full patient immune response profile when trying to determine the effect of a single immune cell on patient outcome. The study later validates this idea by showing that for several tumor types, the beneficial patient survival effects of "good" (tumor-killing) immune infiltration can be modulated by infiltration from immunosuppressive cell types.

The study additionally examines what causes patients to have different immune infiltration patterns and finds that tumor types with a higher average mutation count tend to have higher immune infiltration. However, when looking within a single cancer type, mutation count was not associated with increased mutation burden, suggesting that other factors may drive the immune infiltration differences between patients with the same type of tumor.

"Our study uses a computational method that can be cheaply and easily applied to patient gene expression profiles to explore patients' baseline tumor immune response" explains Varn. "This information can eventually be used to help identify patients likely to respond to certain immunotherapeutic approaches, as baseline immune infiltration of certain cell types has been implicated as a predictor of response to numerous immunotherapeutic approaches."

Looking ahead, the team hopes to use their method to predict which are likely to respond to immunotherapy. To accomplish this, they will need patient datasets that include both the gene expression information that their method uses to infer a patient's immune infiltration profile, and immunotherapy response information. Currently, very few of these datasets have been made publicly available. However, as immunotherapeutic approaches continue to develop, Varn and his team anticipate more of these datasets will be made available, allowing them to eventually use their method to predict immunotherapy responders. "Our study is the first, to our knowledge, that uses computational approaches to examine the effect different immune cells have on each other in the context of the tumor and outline how these interactions affect patient survival" said Varn.

A patient's personal profile can greatly affect their prognosis and can likely affect their response to immunotherapeutic approaches. It is not enough to simply measure the levels of one cell type, as other cell types likely affect cell behavior in the tumor. Understanding how to increase tumor-killing cell activity and decrease immunosuppressive cell activity will be an important question to answer going forward.

Explore further: Silencing cancer cell communication may reduce the growth of tumors

More information: Frederick S. Varn et al, Systematic Pan-Cancer Analysis Reveals Immune Cell Interactions in the Tumor Microenvironment, Cancer Research (2017). DOI: 10.1158/0008-5472.CAN-16-2490

Related Stories

Silencing cancer cell communication may reduce the growth of tumors

January 30, 2017
In several types of cancer, elevated expression of the chemokine receptor CCR4 in tumors is associated with poor patient outcomes. Communication through CCR4 may be one mechanism that cancer cells use to create a pro-tumor ...

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 ...

Innate immune landscape in glioblastoma patient tumors

February 25, 2016
Glioblastoma is an extremely aggressive brain tumor with limited treatment options. Recent progress in using immunotherapy-based treatment options in other tumor types has spurred interest in developing approaches that might ...

Researchers use genetics to probe immune system's role in fighting cancer

August 25, 2016
To better understand the immune system's role in the fight against cancer, University of North Carolina Lineberger Comprehensive Cancer Center researchers have searched thousands of tumors for genetic signatures that might ...

Histone deacetylase inhibitors enhance immunotherapy in lung cancer models, researchers say

March 31, 2016
Several new immunotherapeutic antibodies that inhibit checkpoint receptors on T cells to restimulate the immune system to target tumors have been approved to treat advanced stage lung cancer and melanoma; however, only 20 ...

Sorafenib treatment alters immunosuppressive phenotypes in hepatocellular carcinoma

July 21, 2016
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and results from long-term damage and fibrosis, such as is caused by chronic alcohol abuse and viral-induced hepatitis. Patients with advanced HCC are ...

Recommended for you

Alternative splicing, an important mechanism for cancer

September 22, 2017
Cancer, which is one of the leading causes of death worldwide, arises from the disruption of essential mechanisms of the normal cell life cycle, such as replication control, DNA repair and cell death. Thanks to the advances ...

'Labyrinth' chip could help monitor aggressive cancer stem cells

September 21, 2017
Inspired by the Labyrinth of Greek mythology, a new chip etched with fluid channels sends blood samples through a hydrodynamic maze to separate out rare circulating cancer cells into a relatively clean stream for analysis. ...

Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017
Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers ...

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017
Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

Poliovirus therapy induces immune responses against cancer

September 20, 2017
An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that counter's the ability of cancer cells ...

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.