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This article is original by Translational Medicine.
Please indicate the source for reprinting.
Author: Liz Zee Guide: Antihistamines are a commonly used allergy drug, but the team of Chinese Professor Yu Dihua found that the drug can promote T cell activation and inhibit tumor growth To improve the efficacy of cancer immunotherapy
.
If this finding can be verified in clinical research, it will have an impact on clinical practice
.
A new study from The University of Texas MD Anderson Cancer Center found that antihistamines can improve the response to immune checkpoint inhibitors
.
Preclinical studies have shown that histamine receptor H1 (HRH1) plays a role in tumor-associated macrophages (TAM) and inhibits T cell activation in the tumor microenvironment
.
The results of the study were recently published in Cancer Cell, entitled "The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1"
.
https:// If it is indeed effective in prospective clinical trials, then targeting HRH1 may be used as a treatment and checkpoint blockade Combined to overcome immunotherapy resistance and improve treatment results, especially for patients with previous allergies or high plasma histamine levels
.
"While looking for factors that may affect the response of immunotherapy, we were surprised to find that antihistamines (mediators of allergic reactions) are associated with a significant improvement in patient prognosis," said Xiao Yi, co-leader of the study and lecturer in the Department of Tumor Molecular Cytology (transliterated name, Yi Xiao) said Dr
.
"Further studying this relationship, we found that histamine through its receptor HRH1 can promote the immune evasion of cancer cells and resistance to immunotherapy
.
" Antihistamines improve immunotherapy.
Immune checkpoint inhibitors are a type of immunotherapy.
Block certain checkpoint proteins that regulate T cell activity, release T cells to produce an anti-tumor response and eliminate cancer cells
.
Checkpoint blockade can bring long-lasting responses to many patients, but not all patients benefit equally
.
Therefore, people hope to have a deeper understanding of the factors that lead to immunotherapy sensitivity or resistance
.
The research began with researchers investigating whether other commonly used drugs would affect the response of checkpoint inhibitors
.
They retrospectively analyzed the clinical data of patients who were treated with immune checkpoint inhibitors
.
In patients with melanoma and lung cancer, the simultaneous use of antihistamines targeting HRH1 significantly improved the survival prognosis of patients
.
Breast cancer and colon cancer patients also showed similar trends, but due to the relatively small sample size, the data did not reach statistical significance
.
Based on the Cancer Genome Atlas and other published patient cancer data, the research team also found that high expression of HRH1 in tumors is associated with T cell dysfunction, adverse reactions to checkpoint inhibitors, and poor survival prognosis
.
Histamine receptors inhibit T cell activation.
Based on the observed correlation, the researchers tried to clarify the possible impact of HRH1 and its ligand histamine on immune responses
.
They found that both proteins were elevated in the tumor microenvironment, but they did not seem to come from the same source
.
HRH1 is not present in cancer cells, but its expression level is high in M2 macrophages in the tumor microenvironment, which contributes to immunosuppression
.
Cancer cells appear to be the main source of elevated histamine levels in patient samples and cancer cell lines
.
In preclinical models, blocking HRH1 on macrophages by gene knockout or antihistamine therapy reduces the immunosuppressive activity of TAM, promotes T cell activation, and inhibits tumor growth
.
To understand how HRH1 in TAM affects T cell activity, the researchers studied other regulatory receptors on macrophages
.
Blocking HRH1 activity reduces the membrane localization of VISTA, which is an inhibitory receptor that inhibits T cell activation
.
In addition, blocking HRH1 caused extensive changes in gene expression, leading to a transition from M2 type characteristics to a more pro-inflammatory state consistent with M1 type macrophages
.
The data shows that HRH1 plays a role in TAM, driving cells into an immunosuppressive M2 state, and increasing the membrane expression of the inhibitory checkpoint VISTA, which ultimately leads to T cell dysfunction and suppression of anti-tumor responses
.
Targeting HRH1 to enhance the therapeutic effect In preclinical models of breast cancer and melanoma, compared with the use of checkpoint blockade alone, the combined use of antihistamines and checkpoint blockade can enhance the therapeutic effect and prolong survival
.
In addition, antihistamines have achieved similar responses to anti-VISTA antibody treatment in preclinical models and are currently being evaluated in clinical trials
.
In addition, researchers use preclinical models of allergic diseases to study its impact on tumor progression
.
After allergy induction, histamine levels and tumor growth increased relative to the control group
.
However, these effects can be reversed with antihistamine therapy
.
Similarly, the researchers confirmed that there is a correlation between plasma histamine levels in cancer patients and immune checkpoint inhibitor responses
.
These findings suggest that elevated histamine levels, whether due to allergies or the production of cancer cells, may help suppress anti-tumor responses
.
"Our preclinical research results show that antihistamines have the potential to enhance the response to immunotherapy, especially for people with high levels of histamine in the blood.
" ) Said the doctor
.
"We have more work to do, but we are very happy to continue to explore the possible therapeutic applications of antihistamines.
This is a low-cost treatment with minimal side effects
.
" Next, the team is working hard to design a prospective Clinical trials to evaluate the combined use of antihistamines and checkpoint inhibitors in cancer patients
.
Reference materials: https://medicalxpress.
com/news/2021-11-antihistamines-immunotherapy-response-cell.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital
.
Recommendation·Activity [Live Broadcast] Clinical Application and Progress of Whole Exome Sequencing (WES) in Genetic Diseases Practitioners-Single Cell Research Creation Camp (Guangzhou Station) Popular·Articles Tumor Research [eLife] Benign Mole Degeneration For malignant melanoma, what happened in the middle? Gut Microorganisms [BMJ Sub-Journal] Why do good foods suddenly become intolerant? New research has identified a unique profile of gut bacteria that is highly sensitive to dietary therapy for irritable bowel syndrome, the new coronavirus [Nature sub-Journal] Human genetics perspective-how genetic mutations affect our immune cells, resulting in different severity of COVID-19 Virus [Nature Sub-Journal] Appropriate vitamin D supplementation can fight inflammation, including new coronary pneumonia! Cancer Research [Cell Sub-Journal] MIT researchers have discovered a secret way to fight tumors-wear tumor cell vests and kill tumor cells! Basic research [Nature Sub-Journal] is amazing! 3D images of mouse skulls help scientists create new bones! Basic research [ATS Sub-Journal] Breakthrough! To map the most comprehensive molecular roadmap of human lung proteins, scientists identified and measured 8,938 proteins!
Please indicate the source for reprinting.
Author: Liz Zee Guide: Antihistamines are a commonly used allergy drug, but the team of Chinese Professor Yu Dihua found that the drug can promote T cell activation and inhibit tumor growth To improve the efficacy of cancer immunotherapy
.
If this finding can be verified in clinical research, it will have an impact on clinical practice
.
A new study from The University of Texas MD Anderson Cancer Center found that antihistamines can improve the response to immune checkpoint inhibitors
.
Preclinical studies have shown that histamine receptor H1 (HRH1) plays a role in tumor-associated macrophages (TAM) and inhibits T cell activation in the tumor microenvironment
.
The results of the study were recently published in Cancer Cell, entitled "The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1"
.
https:// If it is indeed effective in prospective clinical trials, then targeting HRH1 may be used as a treatment and checkpoint blockade Combined to overcome immunotherapy resistance and improve treatment results, especially for patients with previous allergies or high plasma histamine levels
.
"While looking for factors that may affect the response of immunotherapy, we were surprised to find that antihistamines (mediators of allergic reactions) are associated with a significant improvement in patient prognosis," said Xiao Yi, co-leader of the study and lecturer in the Department of Tumor Molecular Cytology (transliterated name, Yi Xiao) said Dr
.
"Further studying this relationship, we found that histamine through its receptor HRH1 can promote the immune evasion of cancer cells and resistance to immunotherapy
.
" Antihistamines improve immunotherapy.
Immune checkpoint inhibitors are a type of immunotherapy.
Block certain checkpoint proteins that regulate T cell activity, release T cells to produce an anti-tumor response and eliminate cancer cells
.
Checkpoint blockade can bring long-lasting responses to many patients, but not all patients benefit equally
.
Therefore, people hope to have a deeper understanding of the factors that lead to immunotherapy sensitivity or resistance
.
The research began with researchers investigating whether other commonly used drugs would affect the response of checkpoint inhibitors
.
They retrospectively analyzed the clinical data of patients who were treated with immune checkpoint inhibitors
.
In patients with melanoma and lung cancer, the simultaneous use of antihistamines targeting HRH1 significantly improved the survival prognosis of patients
.
Breast cancer and colon cancer patients also showed similar trends, but due to the relatively small sample size, the data did not reach statistical significance
.
Based on the Cancer Genome Atlas and other published patient cancer data, the research team also found that high expression of HRH1 in tumors is associated with T cell dysfunction, adverse reactions to checkpoint inhibitors, and poor survival prognosis
.
Histamine receptors inhibit T cell activation.
Based on the observed correlation, the researchers tried to clarify the possible impact of HRH1 and its ligand histamine on immune responses
.
They found that both proteins were elevated in the tumor microenvironment, but they did not seem to come from the same source
.
HRH1 is not present in cancer cells, but its expression level is high in M2 macrophages in the tumor microenvironment, which contributes to immunosuppression
.
Cancer cells appear to be the main source of elevated histamine levels in patient samples and cancer cell lines
.
In preclinical models, blocking HRH1 on macrophages by gene knockout or antihistamine therapy reduces the immunosuppressive activity of TAM, promotes T cell activation, and inhibits tumor growth
.
To understand how HRH1 in TAM affects T cell activity, the researchers studied other regulatory receptors on macrophages
.
Blocking HRH1 activity reduces the membrane localization of VISTA, which is an inhibitory receptor that inhibits T cell activation
.
In addition, blocking HRH1 caused extensive changes in gene expression, leading to a transition from M2 type characteristics to a more pro-inflammatory state consistent with M1 type macrophages
.
The data shows that HRH1 plays a role in TAM, driving cells into an immunosuppressive M2 state, and increasing the membrane expression of the inhibitory checkpoint VISTA, which ultimately leads to T cell dysfunction and suppression of anti-tumor responses
.
Targeting HRH1 to enhance the therapeutic effect In preclinical models of breast cancer and melanoma, compared with the use of checkpoint blockade alone, the combined use of antihistamines and checkpoint blockade can enhance the therapeutic effect and prolong survival
.
In addition, antihistamines have achieved similar responses to anti-VISTA antibody treatment in preclinical models and are currently being evaluated in clinical trials
.
In addition, researchers use preclinical models of allergic diseases to study its impact on tumor progression
.
After allergy induction, histamine levels and tumor growth increased relative to the control group
.
However, these effects can be reversed with antihistamine therapy
.
Similarly, the researchers confirmed that there is a correlation between plasma histamine levels in cancer patients and immune checkpoint inhibitor responses
.
These findings suggest that elevated histamine levels, whether due to allergies or the production of cancer cells, may help suppress anti-tumor responses
.
"Our preclinical research results show that antihistamines have the potential to enhance the response to immunotherapy, especially for people with high levels of histamine in the blood.
" ) Said the doctor
.
"We have more work to do, but we are very happy to continue to explore the possible therapeutic applications of antihistamines.
This is a low-cost treatment with minimal side effects
.
" Next, the team is working hard to design a prospective Clinical trials to evaluate the combined use of antihistamines and checkpoint inhibitors in cancer patients
.
Reference materials: https://medicalxpress.
com/news/2021-11-antihistamines-immunotherapy-response-cell.
html Note: This article aims to introduce medical research progress and cannot be used as a reference for treatment options
.
If you need health guidance, please go to a regular hospital
.
Recommendation·Activity [Live Broadcast] Clinical Application and Progress of Whole Exome Sequencing (WES) in Genetic Diseases Practitioners-Single Cell Research Creation Camp (Guangzhou Station) Popular·Articles Tumor Research [eLife] Benign Mole Degeneration For malignant melanoma, what happened in the middle? Gut Microorganisms [BMJ Sub-Journal] Why do good foods suddenly become intolerant? New research has identified a unique profile of gut bacteria that is highly sensitive to dietary therapy for irritable bowel syndrome, the new coronavirus [Nature sub-Journal] Human genetics perspective-how genetic mutations affect our immune cells, resulting in different severity of COVID-19 Virus [Nature Sub-Journal] Appropriate vitamin D supplementation can fight inflammation, including new coronary pneumonia! Cancer Research [Cell Sub-Journal] MIT researchers have discovered a secret way to fight tumors-wear tumor cell vests and kill tumor cells! Basic research [Nature Sub-Journal] is amazing! 3D images of mouse skulls help scientists create new bones! Basic research [ATS Sub-Journal] Breakthrough! To map the most comprehensive molecular roadmap of human lung proteins, scientists identified and measured 8,938 proteins!
