Enhancing Tumor Immunotherapy: The Potential of IL-7-Fc Fusion in Monotherapy and Combined Treatments

Significant advancements in the field of cancer immunotherapy have been made in the past decade, particularly with the introduction of immune checkpoint blockades. The role of immune-related environment modulation in enhancing cancer treatment effectiveness has been recognized. Interleukin-7 (IL-7), a cytokine crucial for lymphocyte development and maintenance, has shown potential as an immunotherapeutic agent. However, its short half-life has been a challenge.

Our study explored the impact of a modified version of human IL-7, fused with hybrid Fc (IL-7-hyFc), on tumor growth in mice. We found that a single injection of IL-7-hyFc significantly reduced tumor growth and increased the expression of CXCR3 on T cells, as well as the presence of CD8+ tumor-infiltrating lymphocytes (TILs). This treatment also reduced the proportion of PD-1+CD8+ TILs and lowered PD-1 expression levels, promoting the expansion and functionality of tumor antigen-specific CD8+ effector T cells.

However, the inhibitory effect on tumor growth was not observed in mice with extensive tumor burdens. To address this, we combined IL-7-hyFc with cyclophosphamide (CTX), a chemotherapy drug, to induce immunogenic cell death without severely affecting the immune system. This combination therapy led to increased CD8+ TIL infiltration and improved survival rates in mice with large tumors.

In conclusion, IL-7-hyFc can effectively combat tumors by revitalizing CD8+ T lymphocytes. While its efficacy is limited in cases of high tumor burden, it can be enhanced when combined with chemotherapy. These findings suggest that IL-7-hyFc could be a valuable addition to various cancer immunotherapy strategies, either as a standalone treatment or in combination with conventional chemotherapy and immunotherapies such as immune checkpoint blockades.

Reference: Kim J-H, Choi D, Ji M K, et al. Preclinical evaluation of the anti-tumor activity of Fc-fused interleukin-7 in both monotherapy and combination therapy [abstract]. Cancer Res 2018;78(13 Suppl):Abstract nr 1731.