1. IL-7 coupled with IL-12 increases intratumoral T cell clonality, leading to complete regression of non-immunogenic tumors.
- Author
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Tasaki M, Yamashita M, Arai Y, Nakamura T, and Nakao S
- Subjects
- A549 Cells, Animals, B7-H1 Antigen immunology, CTLA-4 Antigen immunology, Cell Line, Tumor, Humans, Immunotherapy methods, Lymphocytes, Tumor-Infiltrating immunology, Male, Mice, Mice, Inbred C57BL, Neoplasms therapy, Programmed Cell Death 1 Receptor immunology, Receptors, Antigen, T-Cell immunology, CD8-Positive T-Lymphocytes immunology, Interleukin-12 immunology, Interleukin-7 immunology, Neoplasms immunology
- Abstract
Immune checkpoint inhibitors against PD-1, PD-L1 and CTLA-4 have altered the treatment paradigm for various types of cancers in the past decade. However, they offer clinical benefits to only a subset of patients. Evaluation and identification of an appropriate therapeutic approach to improve intratumoral immune status are needed for better treatment outcomes. We previously demonstrated that intratumoral expression of IL-7 and IL-12 increased tumor-infiltrating lymphocytes in poorly immunogenic tumors, resulting in a higher tumor regression rate than IL-12 alone. However, the mechanism underlying the difference in efficacy with and without IL-7 remains unclear. Here, we identified a previously unknown effect of IL-7 on the T cell receptor (TCR) repertoire of intratumoral CD8
+ T cells, which is induced in the presence of IL-12. While IL-7 alone increased the diversity of intratumoral CD8+ T cells, IL-7 with IL-12 increased a limited number of high-frequency clones, conversely augmenting IL-12 function to increase the clonality. The proportion of mice with multiple high-frequency clones in tumors correlated with that achieving complete tumor regression in efficacy studies. These findings provide a scientific rationale for combining IL-7 and IL-12 in anticancer immunotherapy and unveil a novel IL-7 function on intratumoral TCR repertoire., (© 2021. The Author(s).)- Published
- 2021
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