{"entity":{"id":"idea-bio2-cxcr2-neutrophil-blockade","kind":"idea","name":"Clear the suppressive neutrophils out of pancreatic tumours first","aka":[],"tldr":"Pancreatic tumours are packed with a type of white blood cell that shuts down the immune attack. Blocking the signal that recruits them may open the tumour to immunotherapy.","summary":"CXCR2-dependent recruitment of granulocytic myeloid-derived suppressor cells is a dominant immunosuppressive mechanism in pancreatic and some head and neck cancers, and CXCR2 inhibition plus checkpoint blockade improved survival in genetically engineered mouse models. Human trials of CXCR1/2 inhibitors with chemotherapy or checkpoint blockade have been small and biomarker-light. The decisive step is patient selection by neutrophil infiltration measured on tissue, not by blood counts alone.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Cold tumours and the immunosuppressive microenvironment): Haslam & Prasad, Estimation of the percentage of US patients eligible for and responding to checkpoint inhibitors (JAMA Netw Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["pancreatic","head-and-neck"],"sections":[],"technologies":["checkpoint-inhibitor","digital-pathology-ai","single-cell-spatial"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["cold-vs-hot","desmoplasia"],"trials":[],"people":[],"bottlenecks":["b-tme-immunosuppression","b-immunotherapy-response"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In tumours pre-selected for high granulocytic myeloid infiltration on baseline biopsy, CXCR2 blockade plus checkpoint therapy reduces intratumoural neutrophil density by half and produces objective responses in a population where checkpoint therapy alone gives almost none.","rationale":"The mechanism is one of the best supported in autochthonous pancreatic models, and the intervention is a small molecule with an established safety profile from inflammatory disease programmes.","test":"Biopsy-selected phase 2 with paired tissue myeloid quantification as primary endpoint and response as secondary; abandon if neutrophil density does not fall despite adequate exposure.","maturity":"early-clinical","actor":"industry","cost":"medium","horizonYears":6},"route":"/ideas/idea-bio2-cxcr2-neutrophil-blockade/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"digital-pathology-ai","kind":"technology","name":"Digital pathology & AI","route":"/technologies/digital-pathology-ai/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}