Victoria Cerda, Bobbie J Rimel, Jacob Mercer, Michael A Thompson, Denise Shieh, Emma L Barber, Summer Dewdney, Ritu Salani, Ana I Tergas, Katherine Tucker, Mitchell Kamrava
{"title":"探索性评估原发性和转移性宫颈癌的躯体和免疫景观，以更好地为未来的临床试验发展提供信息。","authors":"Victoria Cerda, Bobbie J Rimel, Jacob Mercer, Michael A Thompson, Denise Shieh, Emma L Barber, Summer Dewdney, Ritu Salani, Ana I Tergas, Katherine Tucker, Mitchell Kamrava","doi":"10.1016/j.ijgc.2025.102677","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To explore the somatic and immunologic landscape of cervical primary versus metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications.</p><p><strong>Methods: </strong>Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intratumor abundance. Immune cell percentages, tumor mutational burden, and tumor neoantigen burden (tumor mutational burden) were compared across tumor sites. χ<sup>2</sup>/Fisher exact tests or Kruskal-Wallis tests were used to assess statistical significance.</p><p><strong>Results: </strong>The median cohort age was 52 years (interquartile range; 42-60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p = .7) of patients. High microsatellite instability (MSI) was noted in 1.5% (p = .7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p = .8) of patients. Median tumor neoantigen burden was 1.71 (interquartile range; 0.98-3.20). Liver lesions had the lowest percentage of B cells (p = .001) and a higher percentage of macrophages (p = .053) compared with other sites. There was a trend toward lower percentages of CD4 cells (p = .053) and natural killer cells (p = .090) in lymph nodes compared with other sites. PIK3CA was the most common pathogenic somatic alteration but not statistically different across sites (q = 0.9).</p><p><strong>Conclusions: </strong>Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.</p>","PeriodicalId":14097,"journal":{"name":"International Journal of Gynecological Cancer","volume":"35 12","pages":"102677"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development.\",\"authors\":\"Victoria Cerda, Bobbie J Rimel, Jacob Mercer, Michael A Thompson, Denise Shieh, Emma L Barber, Summer Dewdney, Ritu Salani, Ana I Tergas, Katherine Tucker, Mitchell Kamrava\",\"doi\":\"10.1016/j.ijgc.2025.102677\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>To explore the somatic and immunologic landscape of cervical primary versus metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications.</p><p><strong>Methods: </strong>Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intratumor abundance. Immune cell percentages, tumor mutational burden, and tumor neoantigen burden (tumor mutational burden) were compared across tumor sites. χ<sup>2</sup>/Fisher exact tests or Kruskal-Wallis tests were used to assess statistical significance.</p><p><strong>Results: </strong>The median cohort age was 52 years (interquartile range; 42-60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p = .7) of patients. High microsatellite instability (MSI) was noted in 1.5% (p = .7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p = .8) of patients. Median tumor neoantigen burden was 1.71 (interquartile range; 0.98-3.20). Liver lesions had the lowest percentage of B cells (p = .001) and a higher percentage of macrophages (p = .053) compared with other sites. There was a trend toward lower percentages of CD4 cells (p = .053) and natural killer cells (p = .090) in lymph nodes compared with other sites. PIK3CA was the most common pathogenic somatic alteration but not statistically different across sites (q = 0.9).</p><p><strong>Conclusions: </strong>Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.</p>\",\"PeriodicalId\":14097,\"journal\":{\"name\":\"International Journal of Gynecological Cancer\",\"volume\":\"35 12\",\"pages\":\"102677\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Gynecological Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ijgc.2025.102677\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Gynecological Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ijgc.2025.102677","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Exploratory evaluation of the somatic and immunologic landscape of primary and metastatic cervical cancer to better inform future clinical trial development.
Objective: To explore the somatic and immunologic landscape of cervical primary versus metastatic tumors for differential sensitivity of metastatic cervical sites and potential therapeutic implications.
Methods: Patients with sequenced squamous cell cervical cancer were selected from the Tempus Database (2016-2023). The cohort included 136 unmatched samples (73 primary, 63 metastatic sites). Pathogenic somatic mutations and gene expression patterns of immune cells were evaluated for relative intratumor abundance. Immune cell percentages, tumor mutational burden, and tumor neoantigen burden (tumor mutational burden) were compared across tumor sites. χ2/Fisher exact tests or Kruskal-Wallis tests were used to assess statistical significance.
Results: The median cohort age was 52 years (interquartile range; 42-60). High tumor mutational burden (≥ 10 mut/Mb) was seen in 9.6% (9% primary, 0% lung, 17% liver, 17% lymph node, p = .7) of patients. High microsatellite instability (MSI) was noted in 1.5% (p = .7) of patients. PD-L1 status was positive in 78% (76% primary, 88% lung, 71% liver, and 80% lymph node, p = .8) of patients. Median tumor neoantigen burden was 1.71 (interquartile range; 0.98-3.20). Liver lesions had the lowest percentage of B cells (p = .001) and a higher percentage of macrophages (p = .053) compared with other sites. There was a trend toward lower percentages of CD4 cells (p = .053) and natural killer cells (p = .090) in lymph nodes compared with other sites. PIK3CA was the most common pathogenic somatic alteration but not statistically different across sites (q = 0.9).
Conclusions: Molecular and immune profiling of primary and metastatic lesions indicated that liver lesions had a less immunogenic microenvironment. Further interrogation of the molecular landscape across paired samples is needed to better inform the development and use of novel therapies.
期刊介绍：
The International Journal of Gynecological Cancer, the official journal of the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology, is the primary educational and informational publication for topics relevant to detection, prevention, diagnosis, and treatment of gynecologic malignancies. IJGC emphasizes a multidisciplinary approach, and includes original research, reviews, and video articles. The audience consists of gynecologists, medical oncologists, radiation oncologists, radiologists, pathologists, and research scientists with a special interest in gynecological oncology.
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