Abstract
<p>Stronger IFN-β responses to TLR1/2 stimulation associates with longer survival after sip-T therapy. <b>A,</b> HRs ± 95% CIs from a Cox proportional hazards model comparing induction of each cytokine (fold mock control) after TLR1/2 stimulation with PAM<sub>3</sub>CSK<sub>4</sub> for PRIME cohort (left) or KCI cohort (right) vs. survival; *, <i>P</i> < 0.05; arrowheads indicate outlier upper bound CI (KCI cohort only). Supplementary Figure S2A depicts Cox proportional HRs for all treatments and cytokines. <b>B,</b> Survival of patients tested for TLR1/2 responsiveness stratified by median IFN-β induction for PRIME (left) and KCI (right) cohorts; <i>P</i> values are from Mantel–Cox test, HR and 95% CIs are from Mantel–Haenszel test. <b>C,</b> Mean <i>z</i>-scores normalized for each cytokine and treatment were computed for the combined cohort of patients (PRIME and KCI, <i>n</i> = 108), excluding patients that were censored prior to 1,000 days due to incomplete follow-up. <i>Z</i>-scores for patients surviving >1,000 days (<i>n</i> = 47) are shown and reflect enrichment/depletion relative to the broader cohort; asterisk indicates FDR adjusted (within each stimulant group) <i>t</i> test <i>Q</i> < 0.05. <b>D,</b> Fold mock treated MFI values for IFN-β after treatment with TLR1/2 stimulation comparing patients surviving < or > 1,000 days from PRIME (top) or KCI (bottom) subcohorts from <b>C</b>; <i>P</i> values are from unpaired <i>t</i> test and mean + SEM is shown. <b>E,</b> Cox proportional hazards model derived HRs ±95% CI and <i>P</i> values for indicated prognostic features and IFN-β. PSA values were not available for two patients, which were excluded from these analyses (<i>n</i> = 104). See Supplementary Figs. S2 and S3 for extended data. MFI, mean fluorescence intensity.</p>
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