Efineptakin alfa (NT-I7) improves overall survival and induces tertiary lymphoid structures in murine lung tumors

Dinh, T.; Lee, J.; Islam, S.; Nanda, N.; Bjelivuk, D.; Andrews, D.; Zhang, J.; Mani, N. L.; Zhou, J.; Wolfarth, A. A.; Choi, D.; Ahmed, R.; Skitzki, J.; Fang, D.; Guo, W.; Wang, Z.; Obeng, R.

doi:10.1101/2025.09.15.676444

bioRxiv · 10.1101/2025.09.15.676444

Efineptakin alfa (NT-I7) improves overall survival and induces tertiary lymphoid structures in murine lung tumors

Dinh, T.·Lee, J.·Islam, S.·Nanda, N.·Bjelivuk, D.·Andrews, D.·Zhang, J.·Mani, N. L.·Zhou, J.·Wolfarth, A. A.·Choi, D.·Ahmed, R.·Skitzki, J.·Fang, D.·Guo, W.·Wang, Z.·Obeng, R.

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Abstract

Tertiary lymphoid structures (TLSs) are emerging as good predictive biomarkers of response to cancer immunotherapy. However, therapeutic strategies to induce these structures are currently limited. We evaluated the therapeutic benefit of efineptakin alfa (NT-I7), a long-acting form of IL-7, and its ability to induce TLSs in a murine lung tumor model. NT-I7 improved overall survival in tumor-bearing mice. It also increased the abundance of T, B, dendritic cells, and stem-like CD8 T cells and promoted the formation of immune aggregates in the tumor microenvironment (TME). Stem-like CD8 T cells were preferentially located in the immune aggregates. Spatial transcriptomic analyses of the TME further demonstrated that the immune aggregates induced by NT-I7 included TLSs with enrichment of Cd274 (PD-L1) transcripts and genes involved in antigen processing and presentation. Upregulation of Cd274 in the TLSs may provide opportunities for synergy between NT-I7 and PD-1-targeted immunotherapy. STATEMENT OF SIGNIFICANCEThis study demonstrates the ability of efineptakin alfa (NT-I7) to potentially augment the clinical efficacy of cancer immunotherapy by inducing tertiary lymphoid structures in the tumor microenvironment.

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Dinh, T., Lee, J., Islam, S., Nanda, N., Bjelivuk, D., Andrews, D., Zhang, J., Mani, N. L., Zhou, J., Wolfarth, A. A., Choi, D., Ahmed, R., Skitzki, J., Fang, D., Guo, W., Wang, Z., Obeng, R.. 2025-09-18. Efineptakin alfa (NT-I7) improves overall survival and induces tertiary lymphoid structures in murine lung tumors. https://doi.org/10.1101/2025.09.15.676444

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