Macrophage transcriptome in response to alphavirus

Reprogramming tumour-associated macrophages (TAMs) into an anti-tumorigenic phenotype using viral immunotherapy vectors is a promising strategy, yet the mechanisms underlying macrophage polarisation in response to replication-deficient viral vectors remain poorly understood. Alphaviral vectors, such as those derived from Semliki Forest virus (SFV), efficiently deliver therapeutic genes due to their cancer tropism and high transgene expression. While SFV vectors do not directly infect macrophages, they may modulate macrophage function via infected cancer cells, cytokine delivery, and alterations in extracellular signalling. In this study, murine mammary cancer cells were infected with SFV vectors engineered to express tumour necrosis factor-a (TNFa) or interferon-? (IFN?). RNA sequencing of macrophages treated with supernatants from SFV/TNFa- and SFV/IFN?-infected cancer cells was performed. All animal experimental protocols were approved by the Latvian Animal Protection Ethical Committee of Food and Veterinary Service (Permit Nr. 93, from 11 December 2017, Riga, Latvia).