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Tumor eradication by hetIL-15 locoregional administration is related to intratumoral accumulation of a novel CD103intCD11b+dendritic cell population

ABSTRACT: Locoregional monotherapy with heterodimeric IL-15 (hetIL-15) in a triple-negative breast cancer (TNBC) orthotopic mouse model resulted in tumor eradication in 40% of treated mice, reduction of metastasis and induction of immunological memory against breast cancer cells. hetIL-15 re-shaped the tumor microenvironment by promoting the intratumoral accumulation of cytotoxic lymphocytes, conventional type 1 dendritic cells (cDC1s) and a novel DC population expressing both CD103 and CD11b markers. These CD103intCD11b+DCs share phenotypic and gene expression characteristics with both cDC1s and cDC2s, have transcriptomic profiles more similar to monocyte derived DCs (moDCs) and correlate with tumor regression. Therefore, hetIL-15, a cytokine directly affecting lymphocytes and inducing cytotoxic cells, has also an indirect rapid and significant effect on the recruitment of myeloid cells, initiating a cascade for tumor elimination though innate and adoptive immune mechanisms. The intratumoral CD103intCD11b+DC population induced by hetIL-15 may be targeted for the development of additional cancer immunotherapy approaches.

ORGANISM(S): Mus musculus

PROVIDER: GSE226932 | GEO | 2023/03/27

REPOSITORIES: GEO

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Complete tumor regression by hetIL-15 locoregional administration is associated with a novel intratumoral CD103intCD11b+ dendritic cell population

Project description:Locoregional administration of heterodimeric IL-15 (hetIL-15) in a triple-negative breast cancer (TNBC) mouse model resulted in tumor eradication in 40% of treated mice, reduction of metastasis and induction of immunological memory against breast cancer cells. hetIL-15 re-shaped the tumor microenvironment by promoting the intratumoral accumulation of cytotoxic lymphocytes, conventional type 1 dendritic cells (cDC1) and a distinct DC population expressing both CD11b and CD103. These CD103intCD11b+DC share phenotypic and gene expression characteristics of both cDC1 and cDC2, have transcriptomic profile similar to monocyte-derived DC (moDC) and they correlate with tumor regression. Therefore, hetIL-15, a factor directly affecting lymphocytes and inducing cytotoxic cells, has also rapid and significant effects on the recruitment of myeloid cells, initiating a cascade for tumor elimination though innate and adoptive immune mechanisms. Our findings suggest a role for hetIL-15 in the treatment of breast cancer.

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