Unlocking PD‐1 antibody resistance: The MUC1 DNA vaccine augments CD8+ T cell infiltration and attenuates tumour suppression

This is the authors' abstract. We don't add key points for this paper.

In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in‐depth research. 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‐tumoural T‐cell ratios or in the functionality of T‐cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8+ T cells by elevating IFN‐γ 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‐agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro‐immunogenic conditions. This assertion is backed by a raised CD8+/CD4+ T‐cell 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‐cell 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‐cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti‐tumour immunity through the application of innovative therapeutic strategies.