ArticleJournal for immunotherapy of cancer2025
Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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
9 citing papers in PubMed.
- Spatiotemporal dynamics of the host-tumor metabolic interface: Implications for precision nutritional oncology.Genes & diseases · 2026Review
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- Necroptotic cell death and immunomodulator release induced by T-cell engaging anti-lymphoma therapies.Cell death & disease · 2026Article
- Body composition radiomics integrated with machine learning to predict prognosis in advanced NSCLC treated with first-line immunochemotherapy and concurrent radiotherapy.BMC pulmonary medicine · 2026Article
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- Review
- Dual-faced CXCL5 holds the key to unlocking immunotherapy in obese pancreatic cancer.Journal for immunotherapy of cancer · 2025Article
- The Role of Obesity in the Regulation of Immunosuppressive Cell Infiltration and Immunosurveillance in Cancers.Diseases (Basel, Switzerland) · 2025Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundCXCR1/2 inhibitors are being implemented with immunotherapies in PDAC clinical trials. CXC-ligands are a family of cytokines responsible for stimulating these receptors; while typically secreted by activated immune cells, fibroblasts, and even adipocytes, they are also secreted by immune-evasive cancer cells. CXC-ligand release is known to occur in response to inflammatory stimuli. Adipose tissue is an endocrine organ and a source of inflammatory signaling peptides. Importantly, adipose-derived cytokines and chemokines are implicated as potential drivers of tumor cell immune evasion; cumulatively, these findings suggest that targeting CXC-ligands may be beneficial in the context of obesity.
methodsRNA-sequencing of human PDAC cell lines was used to assess influences of adipose conditioned media on the cancer cell transcriptome. The adipose-induced secretome of PDAC cells was validated with ELISA for induction of CXCL5 secretion. Human tissue data from CPTAC was used to correlate IL-1β and TNF expression with both CXCL5 mRNA and protein levels. CRISPR-Cas9 was used to knockout CXCL5 from a murine PDAC KPC cell line to assess orthotopic tumor studies in syngeneic, diet-induced obese mice. Flow cytometry and immunohistochemistry were used to compare the immune profiles between tumors with or without CXCL5. Mice-bearing CXCL5 competent or deficient tumors were monitored for differential tumor size in response to anti-PD-1 immune checkpoint blockade therapy.
resultsHuman adipose tissue conditioned media stimulates CXCL5 secretion from PDAC cells via either IL-1β or TNF; neutralization of both is required to significantly block the release of CXCL5 from tumor cells. Ablation of CXCL5 from tumors promoted an enriched immune phenotype with an unanticipatedly increased number of exhausted CD8 T cells. Application of anti-PD-1 treatment to control tumors failed to alter tumor growth, yet treatment of CXCL5-deficient tumors showed response by significantly diminished tumor mass.
conclusionsIn summary, our findings show that both TNF and IL-1β can stimulate CXCL5 release from PDAC cells in vitro, which correlates with expression in patient data. CXCL5 depletion
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.