cancer-immunotherapy
How does cisplatin boost checkpoint therapy?
Open access · cc by · source: Europe PMC
Cisplatin-triggered tumor ferroptosis polarized N1 neutrophils and remodeled cold NSCLC tumors toward hotter T-cell/Th1 states, synergizing with ferroptosis activators in EGFR-mutant settings.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
Triggering tumor ferroptosis can help checkpoint therapy in cold tumors (preclinical).
In EGFR-mutant NSCLC models, cisplatin-driven tumor ferroptosis polarized N1 neutrophils and supported T-cell/Th1 programs that synergized with immune checkpoint inhibitor therapy.
Evidence for the claim as stated.
Valproic acid can restrain cisplatin-induced tubular ferroptosis in mice, unlike cisplatin’s tumor-ferroptosis story.
In cisplatin AKI mice and tubular cells, VPA (like ferrostatin-1) lowered creatinine/BUN, restored GPX4, and reduced ACSL4-linked lipid peroxidation; GPX4 siRNA wiped out VPA’s protection.
Scope note — cisplatin inducing tumor ferroptosis to help ICI — opposite direction from blocking kidney ferroptosis after cisplatin
Limits the claim's scope: a different population, assay, or outcome.
Cisplatin-induced ferroptosis aided ICI efficacy in cold tumors vs IRE1/JNK blockade reduced ferroptosis-linked kidney I/R injury
Evidence for the claim as stated.
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
Cisplatin-induced ferroptosis aided ICI efficacy in cold tumors vs IRE1/JNK blockade reduced ferroptosis-linked kidney I/R injury
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
History
When this study was placed
Dated entries from the concept change log — when this paper was added or removed as support, challenge, or qualifier on a claim.
Placed as a scope qualifier on Ferroptosis
In cisplatin AKI mice and tubular cells, VPA (like ferrostatin-1) lowered creatinine/BUN, restored GPX4, and reduced ACSL4-linked lipid peroxidation; GPX4 siRNA wiped out VPA’s protection.
Placed as supporting evidence on Ferroptosis
Cisplatin can be used to induce tumor ferroptosis in oncology models and also drives kidney ferroptosis that VPA tries to block. Same molecule, opposite therapeutic aims.
Placed as supporting evidence on Ferroptosis
In EGFR-mutant NSCLC models, cisplatin-driven tumor ferroptosis polarized N1 neutrophils and supported T-cell/Th1 programs that synergized with immune checkpoint inhibitor therapy.
Study at a glance
- Design
- Animal / in-vitro — Tumor-cell ferroptosis, N1 neutrophil polarization, and ICI efficacy after cisplatin
- N
- Preclinical tumor models and cell experiments
- Population
- Tumor cells and mouse tumor-microenvironment models
- Outcome
- ICI efficacy after cisplatin-induced ferroptosis and neutrophil polarization
Structured fields used in claim comparison tables when every cited study has a complete layer.
Inspect source passages
How does cisplatin boost checkpoint therapy?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
Authors report cisplatin→ferroptosis→N1 neutrophils remodeling cold to hot tumors.
In this study, we found that cisplatin induced ferroptosis of tumor cells, followed by N1 neutrophil polarization in the tumor microenvironment, which in turn remodeled the “cold” tumor to a “hot” one through enhancing T-cell infiltration and Th1 differentiation
Clinical chemo-IO context?
first-line treatment for patients with advanced non–small cell lung cancer (NSCLC) with negative driver gene mutations
Key findings
Cisplatin induced tumor-cell ferroptosis then N1 neutrophil polarization that helped convert “cold” to “hot” tumors via T-cell infiltration and Th1 differentiation; ferroptosis activation synergized with chemoimmunotherapy in EGFR-mutant NSCLC models.
Methodology
Studied cisplatin effects on ferroptosis and neutrophil polarization in NSCLC models (including A549/LLC systems), assessed T-cell infiltration/Th1 differentiation, and tested ferroptosis-activator combinations aimed at EGFR-mutant immunotherapy resistance.
Limitations
Mouse/cell mechanisms may not fully predict human EGFR-mutant responses; clinical dosing/schedule optimization was not a randomized patient trial here.
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