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, as well as its ability to remodel the tumor immune microenvironment and induce TLSs in murine lung and colorectal tumor models. 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 TLS-like structures with enrichment of Cd274 (PD-L1) transcripts and genes involved in antigen processing and presentation. Up-regulation of Cd274 in the TLS-like structures may provide opportunities for synergy between NT-I7 and PD-1-targeted immunotherapy.
Dinh et al. (Sun,) studied this question.