Faculty, Staff and Student Publications
Publication Date
8-11-2024
Journal
Nature Communications
Abstract
Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.
Keywords
Humans, Male, Cancer Vaccines, Middle Aged, Female, Waldenstrom Macroglobulinemia, Aged, Tumor Microenvironment, Precision Medicine, Vaccines, DNA, Antigens, Neoplasm, B-Lymphocytes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Hemic and Lymphatic Diseases Commons, Medical Sciences Commons, Neoplasms Commons, Oncology Commons
Comments
Supplementary Materials
Data Availability Statement
PMID: 39128904