SMO mutation affects tumor immuno-microenvironment and predicts the effect of immune checkpoint inhibitor: from NSCLC to multiple-cancers
Abstract A critical and challenging process in immunotherapy is to identify cancer patients who could benefit from immune checkpoint inhibitors (ICIs). Exploration of predictive biomarkers could help to optimize the clinical benefits. SMO mutation was found to be enriched in patients responding to ICIs therapy. In the discovery NSCLC cohort (N = 349), significant differences were detected between SMO_MUT and SMO_WT patients regarding objective response rate (ORR, 53.8% vs. 23.7%, p = 0.021), durable clinical benefit (DCB, 69.2% vs. 35.2%, p = 0.018), and median progression-free survival (PFS, 23.0 m vs. 3.8 m, adjusted p = 0.041), which was further confirmed in the validation NSCLC cohort (PFS, 9.3 m vs. 4.8 m, adjusted p = 0.038). In the pan-cancers cohort (N = 1347), significant overall survival advantage was observed in SMO mutation patients (not reach [NR] vs. 18 m, adjusted p = 0.024). In subgroup analysis, the survival advantage of SMO_MUT vs. SMO_WT was prominent and consistent across gender, age, treatment, cancer type, and TMB (all Pinteraction > 0.05). In further exploring, SMO mutation status was found to be connected with higher tumor mutation burden, more neoantigen load, more DDR mutations, higher MSI score and more CD8+ T cell infiltration. Multiple immune segments including antigen processing and presentation, NK/CD4+/CD8 + T cell and interferon gamma response were found to be activated in SMO_MUT tumors. SMO mutation status was an independent prognostic factor, which can predict better clinical outcomes in ICIs treatment across multiple cancer types..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 27. Mai Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ji, Wenxiang [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-1691028/v1 |
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| PPN (Katalog-ID): |
XRA036124869 |
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| 520 | |a Abstract A critical and challenging process in immunotherapy is to identify cancer patients who could benefit from immune checkpoint inhibitors (ICIs). Exploration of predictive biomarkers could help to optimize the clinical benefits. SMO mutation was found to be enriched in patients responding to ICIs therapy. In the discovery NSCLC cohort (N = 349), significant differences were detected between SMO_MUT and SMO_WT patients regarding objective response rate (ORR, 53.8% vs. 23.7%, p = 0.021), durable clinical benefit (DCB, 69.2% vs. 35.2%, p = 0.018), and median progression-free survival (PFS, 23.0 m vs. 3.8 m, adjusted p = 0.041), which was further confirmed in the validation NSCLC cohort (PFS, 9.3 m vs. 4.8 m, adjusted p = 0.038). In the pan-cancers cohort (N = 1347), significant overall survival advantage was observed in SMO mutation patients (not reach [NR] vs. 18 m, adjusted p = 0.024). In subgroup analysis, the survival advantage of SMO_MUT vs. SMO_WT was prominent and consistent across gender, age, treatment, cancer type, and TMB (all Pinteraction > 0.05). In further exploring, SMO mutation status was found to be connected with higher tumor mutation burden, more neoantigen load, more DDR mutations, higher MSI score and more CD8+ T cell infiltration. Multiple immune segments including antigen processing and presentation, NK/CD4+/CD8 + T cell and interferon gamma response were found to be activated in SMO_MUT tumors. SMO mutation status was an independent prognostic factor, which can predict better clinical outcomes in ICIs treatment across multiple cancer types. | ||
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