单位：[1]Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[2]Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA[3]Enterprise Data Engineering & Analytics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[4]Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[5]Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan[6]Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA[7]Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China[8]Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing, China重庆医科大学附属第一医院[9]Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[10]Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[11]Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China重庆医科大学附属第一医院[12]Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, China临床科室肿瘤中心肿瘤内科首都医科大学附属北京友谊医院
Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. Importantly, cancer patients with low plasma histamine levels had a more than tripled objective response rate to anti-PD-1 treatment compared with patients with high plasma histamine. Altogether, pre-existing allergy or high histamine levels in cancer patients can dampen immunotherapy responses and warrant prospectively exploring antihistamines as adjuvant agents for combinatorial immunotherapy.
基金：
National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01CA112567, R01CA184836, R01CA208213]; NIH Cancer Center support grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P30CA016672]; Cancer Prevention & Research Institute of Texas (CPRIT) [RP180734]; METAVivor grants [56675, 58284]
第一作者单位：[1]Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA[11]Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Hongzhong Li,Yi Xiao,Qin Li,et al.The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1[J].CANCER CELL.2022,40(1):36-+.doi:10.1016/j.ccell.2021.11.002.
APA：
Hongzhong Li,Yi Xiao,Qin Li,Jun Yao,Xiangliang Yuan...&Dihua Yu.(2022).The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1.CANCER CELL,40,(1)
MLA：
Hongzhong Li,et al."The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1".CANCER CELL 40..1(2022):36-+
医学