Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers
BackgroundImmune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients.P...
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.987568/full |
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| author | Yanni Wang Jianling Zou Yun Li Xi Jiao Yujiao Wang Na Zhuo Mengting Gao Jifang Gong Jian Li Xiaotian Zhang Xicheng Wang Zhi Peng Changsong Qi Zhenghang Wang Jie Li Yan Li Lin Shen Henghui Zhang Zhihao Lu |
| author_facet | Yanni Wang Jianling Zou Yun Li Xi Jiao Yujiao Wang Na Zhuo Mengting Gao Jifang Gong Jian Li Xiaotian Zhang Xicheng Wang Zhi Peng Changsong Qi Zhenghang Wang Jie Li Yan Li Lin Shen Henghui Zhang Zhihao Lu |
| author_sort | Yanni Wang |
| collection | DOAJ |
| description | BackgroundImmune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients.Patients and methodsMetastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis.ResultsFifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS.ConclusionsSerological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy. |
| first_indexed | 2024-04-11T21:19:46Z |
| format | Article |
| id | doaj.art-c6fcdb6f36db48fda0006d5277c0fd76 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T21:19:46Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c6fcdb6f36db48fda0006d5277c0fd762022-12-22T04:02:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.987568987568Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancersYanni Wang0Jianling Zou1Yun Li2Xi Jiao3Yujiao Wang4Na Zhuo5Mengting Gao6Jifang Gong7Jian Li8Xiaotian Zhang9Xicheng Wang10Zhi Peng11Changsong Qi12Zhenghang Wang13Jie Li14Yan Li15Lin Shen16Henghui Zhang17Zhihao Lu18Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Medical Affairs, Genecast Precision Medicine Technology Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaInstitute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, ChinaDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, ChinaBackgroundImmune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients.Patients and methodsMetastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis.ResultsFifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS.ConclusionsSerological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.987568/fullgastrointestinal cancersimmune checkpoint inhibitorsimmune-related adverse eventsbiomarkercytokines |
| spellingShingle | Yanni Wang Jianling Zou Yun Li Xi Jiao Yujiao Wang Na Zhuo Mengting Gao Jifang Gong Jian Li Xiaotian Zhang Xicheng Wang Zhi Peng Changsong Qi Zhenghang Wang Jie Li Yan Li Lin Shen Henghui Zhang Zhihao Lu Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers Frontiers in Immunology gastrointestinal cancers immune checkpoint inhibitors immune-related adverse events biomarker cytokines |
| title | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
| title_full | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
| title_fullStr | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
| title_full_unstemmed | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
| title_short | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
| title_sort | serological biomarkers predict immune related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
| topic | gastrointestinal cancers immune checkpoint inhibitors immune-related adverse events biomarker cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.987568/full |
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