DataSheet_1_Immunogenomic correlates of immune-related adverse events for anti–programmed cell death 1 therapy.docx

Despite impressive antitumor efficacy of programmed cell death 1 (PD-1) inhibitors, this inhibition can induce mild to severe autoimmune toxicities, termed immune-related adverse events (irAEs). Yet, predictive pretreatment biomarkers for irAEs development across cancer types remain elusive. We first assessed cellular and molecular factors. To determine factors predicting the risk of irAEs for anti–PD-1 immunotherapy across multiple cancer types, an integrative analysis of cellular and molecular factors from 9104 patients across 21 cancer types and 4865522 postmarketing adverse event reports retrieved from adverse event reporting system was then performed. Accuracy of predictions was quantified as Pearson correlation coefficient determined using leave-one-out cross-validation. Independent validation sets included small cell lung cancer and melanoma cohorts. Out of 4865522 eligible adverse events reports, 10412 cases received anti–PD-1 monotherapy, of which, 2997 (28.78%) exhibited at least one irAE. Among established immunogenomic factors, dendritic cells (DC) abundance showed the strongest correlation with irAEs risk, followed by tumor mutational burden (TMB). Further predictive accuracy was achieved by DC and TMB in combination with CD4+ naive T-cells abundance, and then validated in the small cell lung cancer cohort. Additionally, global screening of multiomics data identified 11 novel predictors of irAEs. Of these, IRF4 showed the highest correlation. Best predictive performance was observed in the IRF4 – TCL1A – SHC-pY317 trivariate model. Associations of IRF4 and TCL1A expression with irAEs development were verified in the melanoma cohort receiving immune checkpoint inhibitors. Collectively, pretreatment cellular and molecular irAEs-associated features as well as their combinations are identified regardless of cancer types. These findings may deepen our knowledge of irAEs pathogenesis and, ultimately, aid in early detection of high-risk patients and management of irAEs.</p

Supplementary Table 1: Impact of ALK fusion variant on clinical outcomes in EML4-ALK NSCLC patients: a systematic review and meta-analysis

Supplementary Table 1: Impact of ALK Fusion Variant on Clinical Outcomes in EML4-ALK NSCLC Patients: a systematic review and meta-analysis.Quality assessment of eligible studies using the Newcastle Ottawa quality assessment scaleAbstractBackground: Emerging studies showed that ALK-fusion variants were associated with heterogeneous clinical outcomes. However, contradicting conclusions drew in some other studies considered no correlation between ALK variants and prognoses. Methods: we performed a systematic review and meta-analysis to evaluated the prognostic value of EML4-ALK fusion variants for the outcome of patients. Results: 28 studies were included in our analysis. According to the pooled results, patients harboring variant 1 showed equivalent PFS and OS with non-v1 (HR for PFS: 0.91(0.68-1.21), p=0.499; for OS: 1.12(0.73-1.72), p=0.610). Similarly, patients with v3 showed the same disease progress with non-v3 (pooled HR for PFS=1.07(0.72-1.58), p=0.741). However, pooled results for OS suggested that patients with v3 had a worse survival than non-v3 (HR=3.44(1.42-8.35), p=0.006). Conclusion: Overall results suggested that patients with v1 exhibited no significant difference with non-v1 in terms of OS and PFS, while v3 was associated with shorter OS in ALK-positive NSCLC patients.</div

Supplementary Figure 1: Impact of ALK fusion variant on clinical outcomes in EML4-ALK NSCLC patients: a systematic review and meta-analysis

Supplementary Figure 1: Impact of ALK Fusion Variant on Clinical Outcomes in EML4-ALK NSCLC Patients: a systematic review and meta-analysis.Sensitivity analyses for overall PFS and OS in ALK-positive NSCLC patients. (A) Overall PFS in v1 vs non-v1; (B) Overall OS in v1 vs non-v1; (C) Overall PFS in v3 vs non-v3; (D) Overall OS in v3 vs non-v3; (E) Overall PFS in short-form variant vs long-form variant; (F) Overall OS in short-form variant vs long-form variant.AbstractBackground: Emerging studies showed that ALK-fusion variants were associated with heterogeneous clinical outcomes. However, contradicting conclusions drew in some other studies considered no correlation between ALK variants and prognoses. Methods: we performed a systematic review and meta-analysis to evaluated the prognostic value of EML4-ALK fusion variants for the outcome of patients. Results: 28 studies were included in our analysis. According to the pooled results, patients harboring variant 1 showed equivalent PFS and OS with non-v1 (HR for PFS: 0.91(0.68-1.21), p=0.499; for OS: 1.12(0.73-1.72), p=0.610). Similarly, patients with v3 showed the same disease progress with non-v3 (pooled HR for PFS=1.07(0.72-1.58), p=0.741). However, pooled results for OS suggested that patients with v3 had a worse survival than non-v3 (HR=3.44(1.42-8.35), p=0.006). Conclusion: Overall results suggested that patients with v1 exhibited no significant difference with non-v1 in terms of OS and PFS, while v3 was associated with shorter OS in ALK-positive NSCLC patients.</div

Each age-group’s mean reaction time and standard deviation<i>(ms)</i>.

Each age-group’s mean reaction time and standard deviation(ms).</p

Procedure of endogenous spatial cuing task of Experiment 1.

Procedure of endogenous spatial cuing task of Experiment 1.</p

Procedure of the exogenous spatial cuing task of Experiment 2.

Procedure of the exogenous spatial cuing task of Experiment 2.</p

Each age group’s SNARC effect for valid cues (upper row) and for invalid cues (lower row).

Panels from left to right show 7-, 9-, 11-year-olds, and adults in each row.</p

Results of interaction about magnitude and hand for each age-group in difference cues.

Results of interaction about magnitude and hand for each age-group in difference cues.</p

Results of ANOVA analyses.

Results of ANOVA analyses.</p

Results of ANOVA analyses.

Results of ANOVA analyses.</p