Intratumoral infection by CMV may change the tumor environment by directly interacting with tumor-associated macrophages to promote cancer immunity

Figures & data

Figure 1. Schematic of Intratumoral CMV therapy. Tumor-associated macrophages (TAM) in tumors help to promote and drive tumor growth. After injecting CMV intratumorally, CMV infected TAMs and this correlated with a delay in tumor growth. Combining this intratumoral CMV infection of TAM with anti-PD-L1 therapy synergized to induce clearance of more than 60% of tumors and long-term protection.

Figure 2. Tumor associate macrophage and changes induced by CMV infection. A) Pro-inflammatory tumor associated macrophages (TAM) express high levels of MHC-I, MHC-II and release pro-inflammatory cytokines. These attributes can contribute to T cell activation and proliferation, and subsequent anti-tumor effects. B) Tumor progression is associated with an accumulation of anti-inflammatory TAMs, which express lower levels of MHC-I, MHC-II and proinflammatory cytokines and increase expression of anti inflammatory cytokines, leading to diminished T cell responses. Additionally, anti-inflammatory TAMS release VEGF, which induces angiogenesis, CCL2, which can induce the accumulation of anti-inflammatory macrophages, and CCL22, which can induce T_REG infiltration. Together, these attributes contribute to tumor progression. C) After IT infection with MCMV, TAM became infected. CMV infection of macrophages is known to promote a shift toward a more pro-inflammatory phenotype. Additionally, CMV encodes its own virally-encoded chemokines, which attract inflammatory macrophages. Thus, although more work is needed to define the changes in TAM, we hypothesize that MCMV infection of TAMs leads to increased T cell activation and proliferation and increased recruitment of pro-inflammatory macrophages to the tumor. Together, these attributes of TAM MCMV infection may shift the tumor microenvironment from anti-inflammatory to pro-inflammatory.