Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer
Abstract Background Prostate cancer is one of the most common cancers in men with notable interpatient heterogeneity. Implications of the immune microenvironment in predicting the biochemical recurrence-free survival (BCRFS) after radical prostatectomy and the efficacy of systemic therapies in prost...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03827-4 |
| _version_ | 1797863656575205376 |
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| author | Sujun Han Taoping Shi Yuchen Liao Dong Chen Feiya Yang Mingshuai Wang Jing Ma Hu Li Yu Xu Tengfei Zhu Wenxi Chen Guoqiang Wang Yusheng Han Chunwei Xu Wenxian Wang Shangli Cai Xu Zhang Nianzeng Xing |
| author_facet | Sujun Han Taoping Shi Yuchen Liao Dong Chen Feiya Yang Mingshuai Wang Jing Ma Hu Li Yu Xu Tengfei Zhu Wenxi Chen Guoqiang Wang Yusheng Han Chunwei Xu Wenxian Wang Shangli Cai Xu Zhang Nianzeng Xing |
| author_sort | Sujun Han |
| collection | DOAJ |
| description | Abstract Background Prostate cancer is one of the most common cancers in men with notable interpatient heterogeneity. Implications of the immune microenvironment in predicting the biochemical recurrence-free survival (BCRFS) after radical prostatectomy and the efficacy of systemic therapies in prostate cancer remain ambiguous. Methods The tumor immune contexture score (TICS) involving eight immune contexture-related signatures was developed using seven cohorts of 1120 patients treated with radical prostatectomy (training: GSE46602, GSE54460, GSE70769, and GSE94767; validation: GSE70768, DKFZ2018, and TCGA). The association between the TICS and treatment efficacy was investigated in GSE111177 (androgen deprivation therapy [ADT]) and EGAS00001004050 (ipilimumab). Results A high TICS was associated with prolonged BCRFS after radical prostatectomy in the training (HR = 0.32, 95% CI 0.24–0.45, P < 0.001) and the validation cohorts (HR = 0.45, 95% CI 0.32–0.62, P < 0.001). The TICS showed stable prognostic power independent of tumor stage, surgical margin, pre-treatment prostatic specific antigen (PSA), and Gleason score (multivariable HR = 0.50, 95% CI 0.39–0.63, P < 0.001). Adding the TICS into the prognostic model constructed using clinicopathological features significantly improved its 1/2/3/4/5-year area under curve (P < 0.05). A low TICS was associated with high homologous recombination deficiency scores, abnormally activated pathways concerning DNA replication, cell cycle, steroid hormone biosynthesis, and drug metabolism, and fewer tumor-infiltrating immune cells (P < 0.05). The patients with a high TICS had favorable BCRFS with ADT (HR = 0.25, 95% CI 0.06–0.99, P = 0.034) or ipilimumab monotherapy (HR = 0.23, 95% CI 0.06–0.81, P = 0.012). Conclusions Our study delineates the associations of tumor immune contexture with molecular features, recurrence after radical prostatectomy, and the efficacy of ADT and immunotherapy. The TICS may improve the existing risk stratification systems and serve as a patient-selection tool for ADT and immunotherapy in prostate cancer. |
| first_indexed | 2024-04-09T22:40:11Z |
| format | Article |
| id | doaj.art-1d2ca882fd3a460e9dc593858ada754a |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T22:40:11Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-1d2ca882fd3a460e9dc593858ada754a2023-03-22T12:13:51ZengBMCJournal of Translational Medicine1479-58762023-03-0121111410.1186/s12967-022-03827-4Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancerSujun Han0Taoping Shi1Yuchen Liao2Dong Chen3Feiya Yang4Mingshuai Wang5Jing Ma6Hu Li7Yu Xu8Tengfei Zhu9Wenxi Chen10Guoqiang Wang11Yusheng Han12Chunwei Xu13Wenxian Wang14Shangli Cai15Xu Zhang16Nianzeng Xing17Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Urology, Chinese PLA General HospitalBurning Rock BiotechDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Urology, Shanxian Central Hospital of Shandong ProvinceBurning Rock BiotechBurning Rock BiotechBurning Rock BiotechBurning Rock BiotechBurning Rock BiotechInstitute of Basic Medicine and Cancer (IBMC), Chinese Academy of SciencesDepartment of Clinical Trial, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Burning Rock BiotechDepartment of Urology, Chinese PLA General HospitalDepartment of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Background Prostate cancer is one of the most common cancers in men with notable interpatient heterogeneity. Implications of the immune microenvironment in predicting the biochemical recurrence-free survival (BCRFS) after radical prostatectomy and the efficacy of systemic therapies in prostate cancer remain ambiguous. Methods The tumor immune contexture score (TICS) involving eight immune contexture-related signatures was developed using seven cohorts of 1120 patients treated with radical prostatectomy (training: GSE46602, GSE54460, GSE70769, and GSE94767; validation: GSE70768, DKFZ2018, and TCGA). The association between the TICS and treatment efficacy was investigated in GSE111177 (androgen deprivation therapy [ADT]) and EGAS00001004050 (ipilimumab). Results A high TICS was associated with prolonged BCRFS after radical prostatectomy in the training (HR = 0.32, 95% CI 0.24–0.45, P < 0.001) and the validation cohorts (HR = 0.45, 95% CI 0.32–0.62, P < 0.001). The TICS showed stable prognostic power independent of tumor stage, surgical margin, pre-treatment prostatic specific antigen (PSA), and Gleason score (multivariable HR = 0.50, 95% CI 0.39–0.63, P < 0.001). Adding the TICS into the prognostic model constructed using clinicopathological features significantly improved its 1/2/3/4/5-year area under curve (P < 0.05). A low TICS was associated with high homologous recombination deficiency scores, abnormally activated pathways concerning DNA replication, cell cycle, steroid hormone biosynthesis, and drug metabolism, and fewer tumor-infiltrating immune cells (P < 0.05). The patients with a high TICS had favorable BCRFS with ADT (HR = 0.25, 95% CI 0.06–0.99, P = 0.034) or ipilimumab monotherapy (HR = 0.23, 95% CI 0.06–0.81, P = 0.012). Conclusions Our study delineates the associations of tumor immune contexture with molecular features, recurrence after radical prostatectomy, and the efficacy of ADT and immunotherapy. The TICS may improve the existing risk stratification systems and serve as a patient-selection tool for ADT and immunotherapy in prostate cancer.https://doi.org/10.1186/s12967-022-03827-4Prostate cancerTumor immune microenvironmentBiochemical recurrenceAndrogen deprivation therapyImmunotherapy |
| spellingShingle | Sujun Han Taoping Shi Yuchen Liao Dong Chen Feiya Yang Mingshuai Wang Jing Ma Hu Li Yu Xu Tengfei Zhu Wenxi Chen Guoqiang Wang Yusheng Han Chunwei Xu Wenxian Wang Shangli Cai Xu Zhang Nianzeng Xing Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer Journal of Translational Medicine Prostate cancer Tumor immune microenvironment Biochemical recurrence Androgen deprivation therapy Immunotherapy |
| title | Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer |
| title_full | Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer |
| title_fullStr | Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer |
| title_full_unstemmed | Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer |
| title_short | Tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer |
| title_sort | tumor immune contexture predicts recurrence after prostatectomy and efficacy of androgen deprivation and immunotherapy in prostate cancer |
| topic | Prostate cancer Tumor immune microenvironment Biochemical recurrence Androgen deprivation therapy Immunotherapy |
| url | https://doi.org/10.1186/s12967-022-03827-4 |
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