ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2026
Baseline IL-6 independently predicts severe immune-related toxicity and poor survival in advanced gastric cancer treated with immunotherapy.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundImmune checkpoint inhibitors (ICIs) improve survival in advanced gastric cancer (GC), yet predicting therapeutic benefit versus toxicity remains challenging. Elevated interleukin-6 (IL-6) is linked to poor prognosis, but whether it simultaneously influences immune-related adverse events (irAEs) and how this relationship impacts survival remains unclear.
methodsWe retrospectively analyzed 244 patients with advanced GC treated with ICIs. Predictors of high-grade irAEs were evaluated using Firth's penalized logistic regression to mitigate small-sample bias. Independent prognostic factors for overall survival (OS) were identified via multivariable Cox analysis and validated using propensity score matching (PSM). Causal mediation analysis was performed to assess whether the effect of IL-6 on OS was mediated through irAEs. Biological mechanisms were explored using TCGA-STAD transcriptomic data.
resultsBaseline IL-6 was a strong independent predictor of high-grade irAEs (OR = 2.74, P < 0.001) and inferior OS (P = 0.019), a finding confirmed after PSM. Mediation analysis did not demonstrate a statistically significant mediating effect of irAEs on the relationship between IL-6 and survival. Bioinformatic validation linked high IL-6 expression to hyper-inflammatory signaling (TNF/IL-17 pathways) and immunosuppressive M2 macrophage infiltration.
conclusionBaseline IL-6 was independently associated with both severe immune-related toxicity and inferior overall survival, suggesting that elevated systemic IL-6 reflects an adverse inflammatory state in which toxicity does not necessarily correspond to improved therapeutic outcomes. These findings support further evaluation of IL-6 in risk stratification and warrant prospective investigation into its potential therapeutic modulation in combination with ICIs.
Indexed as
Identifiers
42572075What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.