CpG-based immunotherapy impairs antitumor activity of BRAF inhibitors in a B-cell-dependent manner

• DOI: 10.1038/onc.2017.35
• Publication Date: 2017-03-06T18:22:40Z
• Authors: L Huang; Z Wang; C Liu; C Xu; R M Mbofung; J A McKenzie; H Khong; P Hwu; W Peng
• Keywords: CpG site; CpG Oligodeoxynucleotide

Combining immunotherapy with targeted therapy has increasingly become an appealing therapeutic paradigm for cancer treatment due to its great potential generating durable and synergistic antitumor response. In this study, however, we unexpectedly found that two types of CpG-based tumor peptide vaccine treatments consistently negated the activity a selective BRAF inhibitor in tumors mutation rather than showing effect. Our further studies demonstrated CpG alone was sufficient dampen inhibitor-induced responses, suggesting impaired observed mice receiving is mainly dependent upon use CpG. Mechanistically, increased number circulating B cells, which produced elevated amounts necrosis factor-α (TNFα) contributed resistance inhibitors. More importantly, B-cell depletion or TNFα neutralization can restore effect inhibition treatment, indicating TNFα-secreting cells play indispensable role induced by Taken together, our results strongly suggest precautions must be implemented when designing combinatorial approaches because distinct regimens, despite their respective benefit as monotherapy, may together provide antagonistic clinical outcomes.