ArticleNature biomedical engineering2021
Cancer-cell stiffening via cholesterol depletion enhances adoptive T-cell immunotherapy.
Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05986981 (Single-arm, Open-label Clinical Study on the Safety, Tolerability, and Preliminary Efficacy of MUC1 Therapeutic Tumor Vaccine in Advanced Solid Cancers), which is not on this map. Cited by 150 papers, 2 of them syntheses that pooled it.
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.
Single-arm, Open-label Clinical Study on the Safety, Tolerability, and Preliminary Efficacy of MUC1 Therapeutic Tumor Vaccine in Advanced Solid Cancers
Who cites it
150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 238 citations in OpenAlex.
- The rise and evolution of cancer mechanobiology: a bibliometric trajectory of three decades of research.Frontiers in pharmacology · 2026Pooled it
- Evaluating cholesterol de novo synthesis biomarkers: a systematic review and meta-analysis of cancer prognosis and clinical outcomes.BMC cancer · 2025Pooled it
- Physiological elasticity and topography modulateiScience · 2026Article
- Nitric-oxide propelled nanomotors sensitize tumors to ferroptosis immunotherapy via cholesterol depletion-induced tumor cells stiffening.Materials today. Bio · 2026Article
- Macrophage Trogocytosis of Tumor Cells Drives the Immunosuppression of Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cofilin1-driven cytoskeletal remodeling modulates pan-cancer CD8Cell reports. Medicine · 2026Article
- Tumor Mechanical Remodeling via Bidirectional Calcium Redistribution Enables Deep Photothermal-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Turning resistance into therapeutic vulnerability: Mechano-reprogramming in cancer.Mechanobiology in medicine · 2026Article
- Phase-Separated Nanoarchitecture of Adhesion-Cytoskeleton Force Coupling Reforms Nuclear Spatiotemporal Posture Conformation and Mechanotransduction of Osteosarcoma on Biofunctional Microarrays.Advanced healthcare materials · 2026Article
- Decoding mechanoregulation in immunological synapses using biomimetic artificial cells.Nature methods · 2026Article
- T cells are blind to the dark mechanics of tumors.Trends open · 2026Review
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.Science advances · 2026Article
- Biochemical reaction-regulated electrocatalytic bipolar electrochemiluminescence platform with immobilization-free and exogenous electroactive-species-free sensing for cholesterol detection.Mikrochimica acta · 2026Article
- Environmentally induced cell stiffening shapes metastatic site selection by tuning the immune vulnerability of cancer cells.Immunity · 2026Article
- Identifying and reprogramming softness-driven cancer stem-like cells overcomes CAR-T cell resistance in solid tumours.Nature biomedical engineering · 2026Article
- Lipids in ovarian cancer ascites impair T cell activation by disrupting TCR dynamics.Nature metabolism · 2026Article
- Cholesterol-depleted macrophage membrane-coated nano-rapamycin for targeted atherosclerosis therapy.Journal of nanobiotechnology · 2026Article
- High-throughput mechanomic screening reveals novel regulators of single-cell mechanics.Biophysical journal · 2026Article
- Ionic regulation of cancer cell stiffness and metastatic colonization via the MRTFA-KCNMB1 axis.Developmental cell · 2026Article
- HMGCS1 drives cholesterol-dependent membrane repair and shields tumor cells from lymphocyte attack.Nature communications · 2026Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Malignant transformation and tumour progression are associated with cancer-cell softening. Yet how the biomechanics of cancer cells affects T-cell-mediated cytotoxicity and thus the outcomes of adoptive T-cell immunotherapies is unknown. Here we show that T-cell-mediated cancer-cell killing is hampered for cortically soft cancer cells, which have plasma membranes enriched in cholesterol, and that cancer-cell stiffening via cholesterol depletion augments T-cell cytotoxicity and enhances the efficacy of adoptive T-cell therapy against solid tumours in mice. We also show that the enhanced cytotoxicity against stiffened cancer cells is mediated by augmented T-cell forces arising from an increased accumulation of filamentous actin at the immunological synapse, and that cancer-cell stiffening has negligible influence on: T-cell-receptor signalling, production of cytolytic proteins such as granzyme B, secretion of interferon gamma and tumour necrosis factor alpha, and Fas-receptor-Fas-ligand interactions. Our findings reveal a mechanical immune checkpoint that could be targeted therapeutically to improve the effectiveness of cancer immunotherapies.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.