Manipulating “Fight or Flight” Could Impact Effectiveness of Immunotherapy for Mesothelioma

Effectiveness of immunotherapy

Doctors at the University of Connecticut may have found a way to influence the effectiveness of immunotherapy by manipulating the body’s fight or flight response. The finding could have a bearing on the treatment of advanced mesothelioma.  

Researchers used mice to confirm the connection between the sympathetic nervous system and the body’s ability to fight off cancer. The sympathetic nervous system regulates the “fight or flight” response to stress. 

The report shows that this response impacts the development of natural killer cells. Drugs that alter that response might change the effectiveness of immunotherapy. 

What is the Sympathetic Nervous System?

When the body is under stress, the sympathetic nervous system (SNS) releases a cascade of hormones and chemicals. These hormones increase alertness and heart rate and send extra blood to the muscles. The University of Connecticut research shows they may also stunt the growth of cancer fighting NK cells. 

“Given the critical functions of NK cells in tumor immunity and their capacity to respond to SNS signals, we hypothesized that SNS input plays a key regulatory role in the NK-mediated anti-tumor response,” explain the study’s authors.

Mesothelioma immunotherapy aims to harness the body’s own anti-tumor response. This includes those NK cells. The effectiveness of immunotherapy depends on a strong immune system response. 

The new study suggests that drugs affecting the SNS could be a problem for mesothelioma patients. These include beta blockers, PARP inhibitors, and some anti-depressants. They may keep immunotherapy from working as well as it should. 

NK Cells and the Effectiveness of Immunotherapy

In the new study, researchers used drugs to change SNS signaling in mice infected with cancer. When they blocked certain aspects of the signal, NK cells did not develop normally. 

Too many immature NK cells accumulated. These cells suppressed immunity in the mice and promoted the growth of their tumors. 

“SNS delivers a critical maturation signal that promotes NK cell development and influences their cytotoxic capacity,” the report concludes.

This kind of response in a person could hamper the effectiveness of mesothelioma treatment. Other studies show that chronic stress can negatively impact immunity by promoting inflammation. But this report suggests that a functional SNS is also critical to the effectiveness of immunotherapy.

“Further characterization of this role will improve our understanding of the consequences of neuroimmune interactions in cancer and inform the development of cancer immunotherapy,” write the authors. 

Many things impact the effectiveness of immune-based mesothelioma therapies. A number of studies suggest that immunotherapy drugs like Keytruda and Opdivo may help other treatments work better. 

Source:

Nevin, JT, et al, “Sympathetic nervous tone limits the development of myeloid-derived suppressor cells”, September 11, 2020, https://immunology.sciencemag.org/content/5/51/eaay9368.full

Nevin, JT, et al, “Sympathetic nervous tone influences the development and function of natural killer cells”, May 1, 2020, The Journal of Immunology, (1 Supplement), https://www.jimmunol.org/content/204/1_Supplement/88.12.abstract

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