Critical immunotherapy target marks dysfunctional regulatory T cells in brain cancer

April 21, 2016, Journal of Clinical Investigation

Immunotherapy represents an exciting advance in cancer treatment that harnesses the immune system to seek and destroy cancer cells. The programmed death 1 (PD-1) pathway dampens immune responses to tumor cells, and several clinical trials have shown favorable outcomes by targeting PD-1 or its ligand PD-1L.

In this issue of JCI Insight, David Hafler and colleagues at Yale University and Massachusetts Institute of Technology examined PD-1-expressing regulatory T cells in glioblastoma multiforme, an extremely aggressive form of brain cancer. Regulatory T cells normally constrain immune responses and keep other types of T cells from mounting hyper-aggressive responses.

Although anti-PD1 therapy is generally thought to promote conventional T cell activity, the Hafler team now reports that PD-1 expression on regulatory T cells from the tumors of glioblastoma multiforme patients correlates with regulatory T cell dysfunction.

They also found that glioblastoma multiforme patients treated with a PD-1 blocking antibody had a higher proportion of dysfunctional regulatory T cells. These observations suggest the possibility that PD-1 targeting therapies could work, in part, by driving further regulatory T .

Future studies will be needed to more fully understand the contribution of this pathway to anti-tumor effects.

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

More information: Daniel E. Lowther et al, PD-1 marks dysfunctional regulatory T cells in malignant gliomas, JCI Insight (2016). DOI: 10.1172/jci.insight.85935

Related Stories

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 ...

Overcoming immune exhaustion from chronic HIV infection

December 3, 2015
Chronic HIV infection results in exhaustion of the immune system, a phenomenon characterized by dysfunctional HIV-specific killer T cells. The exhausted T cells display inhibitory proteins on their surface, and scientists ...

Gene-editing tool can improve efficacy of adoptive T-cell immunotherapy

April 15, 2016
The gene-editing tool TALEN can be used to inactivate PD-1-mediated immunosuppression and enhance the efficacy of a type of immunotherapy called adoptive T-cell transfer against solid tumors, according to a preclinical study ...

Neutralizing a tumor's acidic environment improves activity of immune-targeting cancer therapies

March 17, 2016
Cancer cells have the ability to grow in an acidic tumor environment that is detrimental to other cells, including immune cells. In a Cancer Research cover article published this week, Moffitt Cancer Center reported that ...

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 ...

Adding immunotherapy to RFA may benefit colorectal cancer patients with liver metastasis

March 1, 2016
Radiofrequency ablation (RFA), a procedure to treat liver metastases in patients with colorectal cancer, was found to induce antitumor immune responses in human samples of primary colon tumor, and mice treated with a combination ...

Recommended for you

Mechanism that drives development of liver cancer brought on by non-alcoholic fatty liver disease discovered

April 19, 2018
A team of researchers from several institutions in China has found a mechanism that appears to drive the development of a type of liver cancer not caused by alcohol consumption. In their paper published in the journal Science ...

Discovery adds to evidence that some children are predisposed to develop leukemia

April 19, 2018
St. Jude Children's Research Hospital researchers have made a discovery that expands the list of genes to include when screening individuals for possible increased susceptibility to childhood leukemia. The finding is reported ...

Scientists identify 170 potential lung cancer drug targets using unique cellular library

April 19, 2018
After testing more than 200,000 chemical compounds, UT Southwestern's Simmons Cancer Center researchers have identified 170 chemicals that are potential candidates for development into drug therapies for lung cancer.

Chip-based blood test for multiple myeloma could make bone biopsies a relic of the past

April 19, 2018
The diagnosis and treatment of multiple myeloma, a cancer affecting plasma cells, traditionally forces patients to suffer through a painful bone biopsy. During that procedure, doctors insert a bone-biopsy needle through an ...

Study may explain why some triple-negative breast cancers are resistant to chemotherapy

April 19, 2018
Triple-negative breast cancer (TNBC) is an aggressive form of the disease accounting for 12 to 18 percent of breast cancers. It is a scary diagnosis, and even though chemotherapy can be effective as standard-of-care, many ...

Protein can slow intestinal tumor growth

April 19, 2018
A new mechanism for regulating stem cells in the intestine of fruit flies has been discovered by researchers at Stockholm University. In addition, it was discovered that a certain protein can slow the growth of tumours in ...

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.