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Recently, the emergence of immunotherapy has revolutionized traditional tumour treatment. However, effective treatments for patients exhibiting αPD-1 resistance are still lacking. In our study, a combination of cytosine–phosphate–guanine oligodeoxynucleotides (CpG-ODNs), anti-OX40 and cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) injection in situ systematically generated a robust antitumour immune response in TC1 and B16 cells, which are αPD-1-resistant malignancies. More precisely, this method activates both adaptive and innate immunity. Additionally, in situ vaccination with CpG/αOX40/cGAMP fully activates the production of cytokines. However, the combination of αPD-1 does not improve the efficacy of triple therapy, prompting further questions. Collectively, the combination of CpG/αOX40/cGAMP causes the regression of various αPD-1-resistant tumours through the full mobilization of innate and adaptive immunity. In addition, we explored the therapeutic effect of triple therapy on the αPD-1-sensitive cell line CT26. The results showed that triple therapy could significantly enhance the therapeutic effect of αPD-1, and some mice even achieved complete tumour regression after the combined application of αPD-1 and triple treatment.

Robust immune response stimulated by in situ injection of CpG/αOX40/cGAMP in αPD-1-resistant malignancy