Critical immunotherapy target marks dysfunctional regulatory T cells in brain cancer

April 21, 2016

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

Tracking how multiple myeloma evolves by sequencing DNA in the blood

December 10, 2017
Although people with multiple myeloma usually respond well to treatment, the blood cancer generally keeps coming back. Following genetic changes in how the disease evolves over time will help to understand the disease and, ...

Landmark CAR-T cancer study published

December 10, 2017
Loyola University Medical Center is the only Chicago center that participated in the pivotal clinical trial of a groundbreaking cancer treatment that genetically engineers a patient's immune system to attack cancer cells.

Study finds emojis promising tool for tracking cancer patients' quality of life

December 10, 2017
In findings presented to the American Society of Hematology, Mayo Clinic researchers found that using emojis instead of traditional emotional scales were helpful in assessing patients' physical, emotional and overall quality ...

Study explores use of checkpoint inhibitors after relapse from donor stem cell transplant

December 10, 2017
Immunotherapy agents known as checkpoint inhibitors have shown considerable promise in patients with hematologic cancers who relapse after a transplant with donor stem cells. Preliminary results from the first clinical trial ...

Blood test may help predict which breast cancers will recur

December 8, 2017
A blood test five years after breast cancer treatment helped identify some women who were more likely to relapse, long before a lump or other signs appeared, a preliminary study found.

Alcohol-abuse drug Antabuse kills cancer cells

December 8, 2017
A new study in Nature by an international team including researchers from Karolinska Institutet, reports that the alcohol-abuse drug Antabuse is effective against cancer. The study also identifies a potential mechanism of ...

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.