Antihistamines can improve immunotherapy for cancer patients

Antihistamines can improve immunotherapy for cancer patients

Antihistamine drugs can improve the immunotherapy effect of cancer patients Antihistamine drugs can improve the immunotherapy effect of cancer patients

Since the first checkpoint inhibitor drugs were used to treat cancer 10 years ago, researchers have been working to make them more effective
.

On November 25, a research report published in Cancer Cell stated that over-the-counter second-generation antihistamines seem to improve patients with different types of cancer receiving anti-PD-1/PD-L1 (anti-tumor immune check Point inhibitor) the result of treatment

"We believe that if it is verified in pre-clinical studies, the findings may have an impact on clinical practice
," said Yu Dihua (transliteration), the corresponding author of the paper and professor and interim director of the Department of Molecular and Cellular Oncology at the University of Texas Anderson Cancer Center.

For example, our research shows that testing the amine level of a patient’s plasma tissue before receiving immunotherapy can help doctors determine whether the patient can benefit from antihistamine therapy

The researchers came to this conclusion after observing the effects of 40 common drugs on the efficacy of checkpoint inhibitors
.

These drugs include over-the-counter drugs such as antacids and anti-inflammatory drugs, and prescription drugs such as antibiotics and steroids

The second-generation H1 antihistamines include cetirizine (zitermine), loratadine (criminidine), and fexofenadine (aligra)
.

These drugs can block histamine metabolites released by immune cells and are widely used in cancer treatment.

At the same time, the researchers noticed that some "hot tumor" patients—that is, those with a high rate of cytotoxic T cell infiltration—are generally considered to respond well to immunotherapy, but the survival rate is very low
.

To understand what makes these tumors different, the researchers performed overall gene expression analysis on patient samples

"We found that Histamine Receptor 1 (HRH1) is considered to be one of the most popular subjects in which'heat tumors' are closely related to adverse clinical outcomes,
" said Xiao Yi (transliteration), the co-first author of the paper
.

He is a lecturer in the Department of Molecular and Cellular Oncology and a member of Yu Dihua's laboratory

Since H1 antihistamines can specifically block the binding of histamine to HRH1, the researchers linked the above findings to the results of experiments in mice, pointing out that histamine secreted by cancer and released by allergic reactions, as well as the high level of HRH1 in macrophages Expression inhibits the activation of cytotoxic T cells and confers resistance to immunotherapy, while antihistamines partially rescued all phenotypic mice
.

The researchers also measured pre-treatment plasma histamine levels in patients receiving anti-PD-1 immunotherapy
.

Compared with patients with lower plasma histamine levels, high levels of histamine are significantly associated with adverse effects of anti-PD-1 immunotherapy, which confirms the findings of the mouse experiment

"We were surprised to find that compared with normal cells, almost all cancer cells we tested significantly increased the secretion of histamine
.

" Xiao Yi said, "We knew that allergic reactions would release a large amount of histamine, but we didn't expect anti-tumor immunity.
It has such an amazing inhibitory effect

However, one limitation of this study is that it only focuses on the function of HRH1 expressed by macrophages, and does not focus on the function of HRH1 in other immune and non-immune cells
.
The researchers said that histamine may also have a broader effect on the phenotype and activity of macrophages
.
This is one of the directions they may explore in the future
.

The researchers also pointed out that choosing the right antihistamines for cancer patients is crucial
.
This study shows that compared with the first generation of non-selective H1 antihistamines, only the second generation of H1 antihistamines that specifically target HRH1 can improve the efficacy
.

"Every year tens of millions of people will have allergies
.
But how allergies affect the development and treatment of cancer has not been well studied
.
" Yu Dihua said, "This study only reveals the tip of the iceberg, and we will continue to explore the two diseases.
The relationship between them
.
” (Source: Feng Weiwei, China Science News)

Related paper information: https://doi.
org/10.
1016/j.
ccell.
2021.
11.
002

https://doi.
org/10.
1016/j.
ccell.
2021.
11.
002 https://doi.
org/10.
1016/j.
ccell.
2021.
11.
002