Interleukin 7 therapy changes tumor immune environment to pro-inflammatory through myeloid and T cell interactions [Visium]

Immune checkpoint inhibitors unleash inhibitory signals on effector T cells inflicted by tumor and surrounding stromal cells. Despite the great success of PD-1 inhibitors in a fraction of cancer patients, lack of checkpoint molecule expression and persistence of immunosuppressive cells limit the effects of the therapy. To overcome the limitations, combination therapies or direct stimulation of myeloid cells are being investigated. Nonetheless, combination therapies increase the incidence of side effects, and a single agent co-stimulating T cell and myeloid populations might be a better strategy. Exploring single cell RNA sequencing data from multiple human cancers and mouse tumor model, we found pleiotropic expression of interleukin 7 receptor on T cells, macrophages, and dendritic cells. Treatment of recombinant IL7 induced expansion of effector CD8 T cells along with pro-inflammatory activation of macrophages and dendritic cells. Spatial transcriptomic data revealed strengthen of anti-tumoral interactions between macrophages and T cells by IL7 treatment. Altogether, our results suggest that IL7 therapy is applicable to a broad range of cancer patients. The CT26 colon carcinoma cells (2x10^5 cells) were subcutaneously (s.c.) injected to the Balb/c mice. For the rIL7 treatment group, 10ug of recombinant mouse IL7 (rIL7) was intraperitoneally (i.p.) treated at day 11 and day 13 post-transplantation. Tissue specimens were obtained at day 14-15 then analyzed by flowcytometry, tissue immunostaining, scRNAseq, and spatial transcriptomics platform (Visium, 10x genomics).