Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacy
Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer with a rising incidence globally. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized HCC treatment, yet response rates remain variable. Sex-based disparities in immunotherapy efficacy have become incr...
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| Language: | English |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1607374/full |
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| author | Lei Song Liyan Sun Yuning Ren Yuning Ren Xiaodan Wang Xiaodan Wang Lei Xian |
| author_facet | Lei Song Liyan Sun Yuning Ren Yuning Ren Xiaodan Wang Xiaodan Wang Lei Xian |
| author_sort | Lei Song |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a highly aggressive liver cancer with a rising incidence globally. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized HCC treatment, yet response rates remain variable. Sex-based disparities in immunotherapy efficacy have become increasingly recognized as important factors influencing treatment outcomes in HCC. This review examines the role of biological sex in HCC progression and immunotherapy responses. It discusses the epidemiology of sex differences in HCC incidence, prognosis, and therapeutic outcomes, highlighting the impact of sex hormones, such as estrogen and testosterone, on immune system function and tumor biology. Estrogen’s protective effects, including enhanced T cell activation and improved immune surveillance, contribute to better treatment responses in females, while testosterone’s immunosuppressive effects lead to poorer outcomes in males. The review also explores the influence of the tumor microenvironment, including immune cell composition and macrophage polarization, on treatment efficacy. Emerging evidence suggests that sex-specific factors, including hormonal status, should be considered in clinical trials and personalized treatment strategies. By addressing these disparities, tailored immunotherapeutic approaches could optimize efficacy and minimize toxicity in both male and female HCC patients, ultimately improving overall outcomes. |
| format | Article |
| id | doaj-art-78eaa33cd54c4e489d4d45c98d23118a |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-78eaa33cd54c4e489d4d45c98d23118a2025-08-20T03:09:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.16073741607374Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacyLei Song0Liyan Sun1Yuning Ren2Yuning Ren3Xiaodan Wang4Xiaodan Wang5Lei Xian6Department of Interventional Therapy, The First Hospital of Jilin University, Changchun, ChinaPediatric Outpatient Department, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, The First Hospital of Jilin University, Changchun, ChinaKey Laboratory of Organ Regeneration and Transplantation of Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, The First Hospital of Jilin University, Changchun, ChinaDepartment of Interventional Therapy, The First Hospital of Jilin University, Changchun, ChinaHepatocellular carcinoma (HCC) is a highly aggressive liver cancer with a rising incidence globally. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized HCC treatment, yet response rates remain variable. Sex-based disparities in immunotherapy efficacy have become increasingly recognized as important factors influencing treatment outcomes in HCC. This review examines the role of biological sex in HCC progression and immunotherapy responses. It discusses the epidemiology of sex differences in HCC incidence, prognosis, and therapeutic outcomes, highlighting the impact of sex hormones, such as estrogen and testosterone, on immune system function and tumor biology. Estrogen’s protective effects, including enhanced T cell activation and improved immune surveillance, contribute to better treatment responses in females, while testosterone’s immunosuppressive effects lead to poorer outcomes in males. The review also explores the influence of the tumor microenvironment, including immune cell composition and macrophage polarization, on treatment efficacy. Emerging evidence suggests that sex-specific factors, including hormonal status, should be considered in clinical trials and personalized treatment strategies. By addressing these disparities, tailored immunotherapeutic approaches could optimize efficacy and minimize toxicity in both male and female HCC patients, ultimately improving overall outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1607374/fullsex disparitiesimmunotherapyhepatocellular carcinomaestrogenhormone |
| spellingShingle | Lei Song Liyan Sun Yuning Ren Yuning Ren Xiaodan Wang Xiaodan Wang Lei Xian Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacy Frontiers in Immunology sex disparities immunotherapy hepatocellular carcinoma estrogen hormone |
| title | Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacy |
| title_full | Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacy |
| title_fullStr | Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacy |
| title_full_unstemmed | Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacy |
| title_short | Sex disparities in hepatocellular carcinoma immunotherapy: hormonal and genetic influences on treatment efficacy |
| title_sort | sex disparities in hepatocellular carcinoma immunotherapy hormonal and genetic influences on treatment efficacy |
| topic | sex disparities immunotherapy hepatocellular carcinoma estrogen hormone |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1607374/full |
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