TACC Simulations Advance Cancer Immunotherapy

May 17, 2017

AUSTIN, May 17, 2017 — The body has a natural way of fighting cancer – it’s called the immune system, and it is tuned to defend our cells against outside infections and internal disorder. But occasionally, it needs a helping hand.

Immunotherapy fights cancer by supercharging the immune system’s natural defenses or contributing additional immune elements that can help the body kill cancer cells.

In recent decades, immunotherapy has become an important tool in treating a wide range of cancers, including breast cancer, melanoma and leukemia.

But alongside its successes, scientists have discovered that immunotherapy sometimes has powerful — even fatal — side-effects. Much still needs to be learned about how the immune system fights cancer, and in this area, supercomputers play an important role.

Identifying Patient-Specific Immune Treatments

Not every immune therapy works the same on every patient. Differences in an individual’s immune system may mean one treatment is more appropriate than another. Furthermore, tweaking one’s system might heighten the efficacy of certain treatments.

Researchers from Wake Forest School of Medicine and Zhejiang University in China developed a novel mathematical model to explore the interactions between prostate tumors and common immunotherapy approaches, individually and in combination. In a study published in February 2016 in Nature Scientific Reports, they used their model to predict how prostate cancer would react to four common immunotherapies:

  • Androgen deprivation therapy — used to control prostate cancer cell growth by suppressing or blocking the production and action the hormone androgen in men;
  • Vaccines — which train the immune system to recognize and destroy harmful substances;
  • Treg depletion — where the subpopulation of T cells, which modulate the immune system, are reduced to increase the efficacy of immunotherapy treatments; and
  • IL-2 neutralization — which disables interleukin, a type of signaling molecule in the immune system.

To study the systematic effects of these four treatments, the researchers incorporated data from animal studies into their complex mathematical models and simulated tumor responses to the treatments using the Stampede supercomputer at the Texas Advanced Computing Center (TACC).

Model construction for predicting treatment outcomes of prostate cancer. [Courtesy: Huiming Peng, Weiling Zhao, Hua Tan, Zhiwei Ji, Jingsong Li, King Li & Xiaobo Zhou, Scientific Reports 6, Article number: 21599 (2016)]

“We do a lot of modeling which relies on millions of simulations,” said Jing Su, a researcher at the Center for Bioinformatics and Systems Biology at Wake Forest School of Medicine and assistant professor in the Department of Diagnostic Radiology. “To get a reliable result, we have to repeat each computation at least 100 times. We want to explore the combinations and effects and different conditions and their results.”

The researchers found that the depletion of T Cells and the neutralization of Interleukin 2 can have a stronger effect when combined with androgen deprivation therapy and vaccines.

The study highlights a potential therapeutic strategy that may manage prostate tumor growth more effectively. It also provides a framework for studying tumor-related immune mechanisms and the selection of therapeutic regimens in other types of cancer.

In separate work published in Nature Scientific Reports in July 2016, the team used data-driven methods to identify two distinct groups of breast cancer patients: one that displayed a wide range of immune pathways and could be effectively treated with hormone therapy and chemotherapy; and another that displayed less immunity and was best treated with surgery.

Read the full article at: https://www.tacc.utexas.edu/-/advancing-cancer-immunotherapy-with-computer-simulations-and-data-analysis


Source: Aaron Dubrow, TACC

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