Longitudinal plasma proteomic analysis identifies biomarkers and combinational targets for anti-PD1-resistant cancer patients
Abstract The response rate of anti-PD1 therapy is limited, and the influence of anti-PD1 therapy on cancer patients is unclear. To address these challenges, we conducted a longitudinal analysis of plasma proteomic changes with anti-PD1 therapy in non-small cell lung cancer (NSCLC), alveolar soft part sarcoma (ASPS), and lymphoma patients. We included 339 plasma samples before and after anti-PD1 therapy from 193 patients with NSCLC, ASPS, or lymphoma. The plasma proteins were detected using data-independent acquisition-mass spectrometry and customable antibody microarrays. Differential proteomic characteristics in responders (R) and non-responders (NR) before and after anti-PD1 therapy were elucidated. A total of 1019 proteins were detected using our in-depth proteomics platform and distributed across 10–12 orders of abundance. By comparing the differential plasma proteome expression between R and NR groups, 50, 206, and 268 proteins were identified in NSCLC, ASPS, and lymphoma patients, respectively. Th17, IL-17, and JAK-STAT signal pathways were identified upregulated in NR group, while cellular senescence and transcriptional misregulation pathways were activated in R group. Longitudinal proteomics analysis revealed the IL-17 signaling pathway was downregulated after treatment. Consistently, many proteins were identified as potential combinatorial therapeutic targets (e.g., IL-17A and CD22). Five noninvasive biomarkers (FLT4, SFTPB, GNPTG, F5, and IL-17A) were further validated in an independent lymphoma cohort (n = 39), and another three noninvasive biomarkers (KIT, CCL3, and TNFSF1) were validated in NSCLC cohort (n = 76). Our results provide molecular insights into the anti-PD1 therapy in cancer patients and identify new therapeutic strategies for anti-PD1-resistant patients..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:73 |
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| Enthalten in: |
Cancer immunology immunotherapy - 73(2024), 3 vom: 13. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tan, Qiaoyun [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| BKL: | |
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| Anmerkungen: |
© The Author(s) 2024 |
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| doi: |
10.1007/s00262-024-03631-7 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract The response rate of anti-PD1 therapy is limited, and the influence of anti-PD1 therapy on cancer patients is unclear. To address these challenges, we conducted a longitudinal analysis of plasma proteomic changes with anti-PD1 therapy in non-small cell lung cancer (NSCLC), alveolar soft part sarcoma (ASPS), and lymphoma patients. We included 339 plasma samples before and after anti-PD1 therapy from 193 patients with NSCLC, ASPS, or lymphoma. The plasma proteins were detected using data-independent acquisition-mass spectrometry and customable antibody microarrays. Differential proteomic characteristics in responders (R) and non-responders (NR) before and after anti-PD1 therapy were elucidated. A total of 1019 proteins were detected using our in-depth proteomics platform and distributed across 10–12 orders of abundance. By comparing the differential plasma proteome expression between R and NR groups, 50, 206, and 268 proteins were identified in NSCLC, ASPS, and lymphoma patients, respectively. Th17, IL-17, and JAK-STAT signal pathways were identified upregulated in NR group, while cellular senescence and transcriptional misregulation pathways were activated in R group. Longitudinal proteomics analysis revealed the IL-17 signaling pathway was downregulated after treatment. Consistently, many proteins were identified as potential combinatorial therapeutic targets (e.g., IL-17A and CD22). Five noninvasive biomarkers (FLT4, SFTPB, GNPTG, F5, and IL-17A) were further validated in an independent lymphoma cohort (n = 39), and another three noninvasive biomarkers (KIT, CCL3, and TNFSF1) were validated in NSCLC cohort (n = 76). Our results provide molecular insights into the anti-PD1 therapy in cancer patients and identify new therapeutic strategies for anti-PD1-resistant patients. | ||
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| 700 | 1 | |a Gao, Ruyun |4 aut | |
| 700 | 1 | |a Zhang, Xiaomei |4 aut | |
| 700 | 1 | |a Yang, Jianliang |4 aut | |
| 700 | 1 | |a Xing, Puyuan |4 aut | |
| 700 | 1 | |a Yang, Sheng |4 aut | |
| 700 | 1 | |a Wang, Dan |4 aut | |
| 700 | 1 | |a Wang, Guibing |4 aut | |
| 700 | 1 | |a Wang, Shasha |4 aut | |
| 700 | 1 | |a Yao, Jiarui |4 aut | |
| 700 | 1 | |a Zhang, Zhishang |4 aut | |
| 700 | 1 | |a Tang, Le |4 aut | |
| 700 | 1 | |a Yu, Xiaobo |4 aut | |
| 700 | 1 | |a Han, Xiaohong |0 (orcid)0000-0001-9190-0167 |4 aut | |
| 700 | 1 | |a Shi, Yuankai |0 (orcid)0000-0002-8685-6744 |4 aut | |
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