Dataset Information

CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression.

ABSTRACT: Interleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. Here, we demonstrated that the in vivo injection of recombinant human IL-15 (200?µg/kg) or murine IL-15 (3?µg/kg) to tumor-bearing NOD-SCID-IL2Rg-/- (NSI) mice resulted in increased tumor progression and CD45+ CD11b+ Gr-1+ CD215+ cell expansion in the tumors and spleen. In B16F10-bearing C57BL/6 mice model, we found that murine IL-15 has antitumoral effect since the activation and expansion of CD8+ T cells with murine IL-15 treatment. But no enhanced or reduced tumor growth was observed in mice when human IL-15 was used. However, both murine and human IL-15 promote CD45+ CD11b+ Gr-1+ CD215+ cells expansion. In xenograft tumor models, CD215+ myeloid cells, but not CD215- cells, responded to human IL-15 stimulation and promoted tumor growth. Furthermore, we found that human IL-15 mediated insulin-like growth factor-1 production in CD215+ myeloid cells and blocking IGF-1 reduced the tumor-promoting effect of IL-15. Finally, we observed that higher IGF-1 expression is an indicator of poor prognosis among lung adenocarcinoma patients. These findings provide evidence that IL-15 may promote tumor cell progression via CD215+ myeloid cells, and IGF-1 may be an important candidate that IL-15 facilitates tumor growth.

SUBMITTER: Lin S

PROVIDER: S-EPMC5722806 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression.

Lin Shouheng S Huang Guohua G Xiao Yiren Y Sun Wei W Jiang Yuchuan Y Deng Qiuhua Q Peng Muyun M Wei Xinru X Ye Wei W Li Baiheng B Lin Simiao S Wang Suna S Wu Qiting Q Liang Qiubin Q Li Yangqiu Y Zhang Xuchao X Wu Yilong Y Liu Pentao P Pei Duanqing D Yu Fenglei F Wen Zhesheng Z Yao Yao Y Wu Donghai D Li Peng P

Frontiers in immunology 20171204

Interleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. Here, we demonstrated that the <i>in vivo</i> injection of recombinant human IL-15 (200 µg/kg) or murine IL-15 (3 µg/kg) to tumor-bearing NOD-<i>SCID-IL2Rg-/-</i> (NSI) mice resulted in increased tumor progression and CD45+ CD11b+ Gr-1+ CD215+ cell expansion in the tumors and spleen. In B16F10-bear ...[more]

PMID: 29255466

Similar Datasets

Project description:BackgroundBone metastasis is the leading cause of death in patients with prostate cancer (PCa) and currently has no effective treatment. Disseminated tumor cells in bone marrow often obtain new characteristics to cause therapy resistance and tumor recurrence. Thus, understanding the status of disseminated prostate cancer cells in bone marrow is crucial for developing a new treatment.MethodsWe analyzed the transcriptome of disseminated tumor cells from a single cell RNA-sequencing data of PCa bone metastases. We built a bone metastasis model through caudal artery injection of tumor cells, and sorted the tumor hybrid cells by flow cytometry. We performed multi-omics analysis, including transcriptomic, proteomic and phosphoproteomic analysis, to compare the difference between the tumor hybrid cells and parental cells. In vivo experiments were performed to analyze the tumor growth rate, metastatic and tumorigenic potential, drug and radiation sensitivity in hybrid cells. Single cell RNA-sequencing and CyTOF were performed to analyze the impact of hybrid cells on tumor microenvironment.ResultsHere, we identified a unique cluster of cancer cells in PCa bone metastases, which expressed myeloid cell markers and showed a significant change in pathways related to immune regulation and tumor progression. We found that cell fusion between disseminated tumor cells and bone marrow cells can be source of these myeloid-like tumor cells. Multi-omics showed the pathways related to cell adhesion and proliferation, such as focal adhesion, tight junction, DNA replication, and cell cycle, were most significantly changed in these hybrid cells. In vivo experiment showed hybrid cells had a significantly increased proliferative rate, and metastatic potential. Single cell RNA-sequencing and CyTOF showed tumor-associated neutrophils/monocytes/macrophages were highly enriched in hybrid cells-induced tumor microenvironment with a higher immunosuppressive capacity. Otherwise, the hybrid cells showed an enhanced EMT phenotype with higher tumorigenicity, and were resistant to docetaxel and ferroptosis, but sensitive to radiotherapy.ConclusionTaken together, our data demonstrate that spontaneous cell fusion in bone marrow can generate myeloid-like tumor hybrid cells that promote the progression of bone metastasis, and these unique population of disseminated tumor cells can provide a potential therapeutic target for PCa bone metastasis.

Dataset Information

CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression.

Publications

CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets