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Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26\/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra\u2010tumoural T\u2010cell ratios or in the functionality of T\u2010cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8<jats:sup>+<\/jats:sup> T cells by elevating IFN\u2010\u03b3 and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single\u2010agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro\u2010immunogenic conditions. This assertion is backed by a raised CD8<jats:sup>+<\/jats:sup>\/CD4<jats:sup>+<\/jats:sup> T\u2010cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T\u2010cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T\u2010cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti\u2010tumour immunity through the application of innovative therapeutic strategies.<\/jats:p>","DOI":"10.1111\/sji.13356","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T06:30:17Z","timestamp":1705732217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unlocking PD\u20101 antibody resistance: The MUC1 DNA vaccine augments CD8<sup>+<\/sup> T cell infiltration and attenuates tumour suppression"],"prefix":"10.1111","volume":"99","author":[{"given":"Xiaoqin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences Xi'an Jiaotong University Health Science Center  Xi'an China"},{"name":"The Clinical Laboratory The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an 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