In vitro treatment of CD8+ T cells with interleukin-7 enhances their in vivo anti-tumor capabilities against an animal model of Ehrlich ascites carcinoma

Abstract

Background: Developing optimal strategies for generating T cells capable of effectively controlling tumors is one of the most important prerequisites for the clinical application of adoptive cell therapies in cancer patients. However, the generation of sufficient numbers of tumor-reactive T cells capable of efficient tumor regression and long-term persistence remains a significant impediment to widespread clinical implementation. Aim: The main aim of the present study was to evaluate the beneficial anti-tumor effects of a simplified combinatorial approach that involves a short activation of naive CD8+ T cells with the T cell mitogen concanavalin A (CON-A; 4 ug/mL) and the survival cytokine IL-7 (10 ng/mL), after a single intraperitoneal injection of cyclophosphamide (CTX; 4 mg/mouse) after their adoptive transfer into Ehrlich ascites carcinoma (EAC) tumor-bearing CD1 mice. Results: We found that adoptive transfer of in vitro IL-7-conditioned T cells into EAC-bearing (3-day) mice previously treated with a single dose of CTX induced a delay in the progression of EAC, and the establishment of long-term immunological memory, which has the efficiency to provide full protection for mice against cancer. Our results indicated that in the presence of IL-7, the short-term T-cell receptor signaling mediates promiscuous qualities in naive cytotoxic CD8+T cells. Conclusion: The data indicate that upon the adoptive transfer of IL-7 conditioned T cells into lymphopenic hosts, they were able to eradicate tumors and also to generate long-term tumor-specific memory.