{"apiVersion":"1","version":"sha256:faade27e0b75b2aca6311142ff65347b4dacc153e8d28cbdf0e8a237319331f9","data":{"id":"S7688","title":"Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma","authors":["Darci Phillips","Magdalena Matusiak","Belén Rivero Gutierrez","Salil S Bhate","Graham L Barlow","Sizun Jiang","Janos Demeter","Kimberly S Smythe","Robert H Pierce","Steven P Fling","Nirasha Ramchurren","Martin A Cheever","Yury Goltsev","Robert B West","Michael S Khodadoust","Youn H Kim","Christian M Schürch","Garry P Nolan"],"publishedDate":"2021-11-18","format":"Paper","url":"https://www.ebi.ac.uk/europepmc/webservices/rest/PMC8602403/fullTextXML","summary":"This observational tissue analysis links immune-cell topography to pembrolizumab response in14selected lymphoma patients from an earlier24-patient trial. Seventy regions and large cell counts remain nested within those patients. Assay validation and resampling reuse the same cohort, without an independent clinical test. Several abundance and signature measures were null; the proposed chemokine mechanism is not causally demonstrated. Nolan is a corresponding coauthor/joint supervisor. Published government grants and commercial/patent disclosures remain attributed, without establishing a classified approach or UAP programme.","subjects":["Imaging","Research methods","Government research funding"],"people":["Garry Nolan"],"review":{"label":"Complete specialist supplied XML text; native graphics unreviewed","scope":"Specialist read all 117,768 supplied normalized XML characters in 14 contiguous untruncated returns, including six figure captions, declarations, attachment labels and102reference entries. Root reviewed the complete frozen analytical packet, without full original source or pixel consumption. Six native graphics/PDF,11distinct attachments, data/code, parent trial/cited originals and current correction history remain unreviewed.","gaps":["Six native figure graphics/PDF layouts and original image fine detail","Supplementary figures/tables, Reporting Summary and all attachment bodies","Source Data and aggregate/raw imaging/RNA datasets","Analysis scripts, code execution and reproducibility reanalysis","Previous CITN trial and all 102 cited bodies","Independent prospective validation or new patient test cohort","Current correction/version history and award/contract/patent/company registries","Complete supplied XML text is specialist consumption; root full analytical packet review is separate from complete root original reading. Native figure pixels, supplements and102cited originals remain unreviewed.","Fourteen selected patients, seven responders/seven nonresponders, exclude ten parent-trial patients for insufficient material. Seventy regions, serial sections and117170cells do not increase patient n; selected tissue and variable collection times limit generalization.","Vectra platform comparison,100subsampling iterations and14leave-one-patient-out checks reuse the same cohort. Six-fold gene-model tuning does not establish patient-separated response testing. Internal cutoff0.7908 is not a prospectively validated clinical threshold.","Patient random intercepts address nesting in many comparisons, but selected-region sampling, manual classification, some unadjusted tests, no blinding/prespecified power, highest-density CODEX experiment selection and one Vectra experiment remain limitations.","Null abundance, IFN-gamma/TGF-beta, PD1-subset and CD8-score results, nonsignificant bulkCXCR5 and cross-disease differences remain explicit. CXCL13 recruitment and downstream killing are proposed interpretations, not tested causal interventions.","Nolan’s corresponding author/joint-supervisor role,22NIHidentifiers and DoD/FDA-grouped support are published attributions, not original award agreements or classified access. FDA grouping of DSTL/AGR/00980/01 and repeated F32recipient forms remain unreconciled.","Article declares Nolan/Goltsev Akoya cofounding/stockholding and patent interests, Phillips/Schuerch/Nolan pendingSpatialScore patent, Schuerch EnableMedicine role and Kim Merck funding. These are article-time disclosures, not current registries.","Source117170versus117220cells,56markers versus54antibodies and figure5panel references remain unresolved. Collection/PMC-release dates are not new clinical studies; current substantive corrections are unchecked."]},"familyId":"NOLAN-CTCL-PD1-NATCOMM-2021-26974-6","citationUrl":"https://bioparity.io/sources/S7688","citation":"Darci Phillips, Magdalena Matusiak, Belén Rivero Gutierrez, Salil S Bhate, Graham L Barlow, Sizun Jiang, Janos Demeter, Kimberly S Smythe, Robert H Pierce, Steven P Fling, Nirasha Ramchurren, Martin A Cheever, Yury Goltsev, Robert B West, Michael S Khodadoust, Youn H Kim, Christian M Schürch, Garry P Nolan. Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma. November 18, 2021. BioParity S7688. https://bioparity.io/sources/S7688"}}