Immune markers linked to prognosis in dog B cell lymphoma

Abstract

Only 60% of patients with diffuse large B cell lymphoma are cured following standard of care therapies. While immune contexture is associated with outcomes in patients treated with chemotherapy, immune mechanisms driving differential therapeutic responses remain unclear. Here, we undertook a comparative analysis of dogs with spontaneous B cell lymphoma (BCL), which exhibit similar dichotomies in therapeutic outcome, to identify conserved and species-specific transcriptional and circulating biomarkers associated with remission duration. In addition, we compared treatment naive and relapsed samples to determine how treatment impacts immune contexture at the time of treatment failure. Among eighteen client-owned dogs with aggressive BCL undergoing multi-agent chemotherapy, comparative immune profiling revealed increased T cell transcripts associated with prolonged remissions and, as in humans, IL2RB expression was associated with favorable outcomes. Increased angiogenic markers were associated with shorter remissions. In treatment naive samples, macrophage associated cytokines were increased, whereas multiple T cell-associated transcripts were enriched in relapsed nodes. Collectively, our findings reveal that changes in immune composition are associated with varying chemotherapeutic outcomes in canine BCL and highlight the potential for comparative oncology approaches to identify factors associated with disease progression, providing insight for development and testing of novel therapeutic approaches.