Personalized Neoantigen Vaccines as Early Intervention in Untreated Patients With Lymphoplasmacytic Lymphoma: A Non- Randomized Phase 1 Trial

The median age of all patients was 67, and the majority were male (78%). [...] Overall, the paired analysis showed a reduction in tumor cells in B-cell compartments post-vaccine in six out of the eight patients, a substantial majority (Fig. 1E and Supplementary Fig. [...] Interestingly, like the plasma cell-like clusters, there was also a trend toward downregulation of expression of HLA class II genes post-vaccine in B-cell cluster 2 tumor cells (Fig. 1G). [...] Dot plots of HLA family gene expression by clonal tumor cells pre- and post-vaccine in cluster 2 only. [...] Paradoxically, dichotomous upregulation of the insulin-like growth factor (IGF) signaling axis post-vaccine was inferred by plasma cell, but not mature B cell LPL subpopulations, including both autocrine and paracrine pathways, consistent with a potential Fig. [...] Comparing post- vs. pre-vaccine samples, most of the signaling pathways affected were associated with reductions in monocytic subpopulations, particularly cluster 3 non- classical monocytes, and to a lesser extent cluster 0 classical mono- cytes (Fig. 4D). [...] T cells in the micro- environment also showed a mixed pattern of up- and down-regulation Article Nature Communications| (2024) 15:6874 9of co-inhibitory pathways (Fig. [...] The bioinformatic analysis also identified a predominant role for myeloid cells in the tumor microenvironment as a source of vaccine- induced, downregulated pro-tumoral signaling to LPL cells. The global signaling pathways affected were primarily associated with monocytic, rather than granulocytic or dendritic cell subpopulations, particularly non-classical CD14-CD16+ monocytes, and to a lesser ext [...] Taken together, these results suggest that vaccine therapy was associated with significant reduction of pro-tumoral signaling by myeloid cells in the LPL microenvironment. [...] NetAnalysis_signalingRole_heatmap) and was used to compute the comparison of overall signaling pathways in pre- vs. post-vaccine samples. Circle plots were generated via netVisual_aggregate, vertex.- size = groupSize, respectively.