Immunity decreases the therapeutic efficacy of viral therapy in brain cancer; Research

Researchers have found that immune cells in the body of the patient could result in weakening of viral therapy of a brain tumor called as glioblastoma.

This research has been published online in the journal of Nature Medicine.

Glioblastoma multiforme (Credit: School of Medicine/Washington University in St. Louis)

Patients with glioblastoma have survival time of about 12 months on average and viruses designed to fight against those tumors is found to be the optimal therapy for this type of cancer. However, this study showed that immune cells could impede viral therapy decreasing efficacy of this therapy.

“In this case, clinical trials of oncolytic viruses proved safe for use in the brain, but we noticed substantial numbers of immune cells in brain tumors after treatment,” Senior author and neurosurgeon Dr. E. Antonio Chiocca, who was professor and chair of neurological surgery while at Ohio State University, said.

Researchers have found that immune cells called as natural killer (NK) cells work in the brain against viruses as they do for infection and within hours of the start of viral therapy these cells start working to eliminate those viruses in the brain.

“To understand this process, we went back to the laboratory and showed that NK cells rapidly infiltrate tumors in mice that have been treated with the therapeutic virus. These NK cells also signal other inflammatory cells to come in and destroy the cancer-killing virus in the tumor.” Chiocca added.

Researchers have found that the NK cells start fighting against the viruses when they showed up NKp30 and NKp46 molecules on their surface. These are natural cytotoxicity receptors (NCRs).

“These receptor molecules enable the NK cells to recognize and destroy the anticancer viruses before the viruses can destroy the tumor,” Dr. Michael A. Caligiuri, director of Ohio State’s Comprehensive Cancer Center and CEO of the James Cancer Hospital and Solove Research Institute, and a senior author of the study, said in a statement.

“When we blocked those receptors, the virus has more time to work, and mice with these brain tumors live longer. The next step is to block these molecules on NK cells in glioblastoma patients and see if we can improve their outcome,” Caligiuri, who is also the John L. Marakas Nationwide Insurance Enterprise Foundation Chair in Cancer Research, said.

Researchers have written, “These results demonstrate that glioblastoma virotherapy is limited partially by an antiviral NK cell response involving specific NCRs, uncovering new potential targets to enhance cancer virotherapy.”

Reference:

Christopher A Alvarez-Breckenridge, Jianhua Yu, Richard Price, Jeffrey Wojton, Jason Pradarelli, Hsiaoyin Mao, Min Wei, Yan Wang, Shun He, Jayson Hardcastle, Soledad A Fernandez, Balveen Kaur, Sean E Lawler, Eric Vivier, Ofer Mandelboim, Alessandro Moretta, Michael A Caligiuri, E Antonio Chiocca, (2012). said in a statement Nature Medicine, DOI: 10.1038/nm.3013

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