期刊
FRONTIERS IN IMMUNOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2018.03185
关键词
anti-CD4 mAb; immune checkpoint inhibitor; TCR repertoire; Cancer-Immunity Cycle; Inter-Organ Clone Tracking
类别
资金
- Japan Agency for Medical Research and Development (AMED) [16768526]
- Japan Society for the Promotion of Science (JSPS) KAKENHI [16K08730, 17929396]
- Grants-in-Aid for Scientific Research [16K08730] Funding Source: KAKEN
Depletion of CD4(+) cells using an anti-CD4 monoclonal antibody (anti-CD4 mAb) induces the expansion of tumor-reactive CD8(+) T cells and strong antitumor effects in several murine tumor models. However, it is not known whether the anti-CD4 mAb treatment activates a particular or a broad spectrum of tumor-reactive CD8(+) T cell clones. To investigate the changes in the TCR repertoire induced by the anti-CD4 mAb treatment, we performed unbiased high-throughput TCR sequencing in a B16F10 mouse subcutaneous melanoma model. By Inter-Organ Clone Tracking analysis, we demonstrated that anti-CD4 mAb treatment increased the diversity and combined frequency of CD8(+) T cell clones that overlapped among the tumor, draining lymph node (dLN), and peripheral blood repertoires. Interestingly, the anti-CD4 mAb treatment-induced expansion of overlapping clones occurred mainly in the dLN rather than in the tumor. Overall, the Inter-Organ Clone Tracking analysis revealed that anti-CD4 mAb treatment enhances the mobilization of a wide variety of tumor-reactive CD8(+) T cell clones into the Cancer-Immunity Cycle and thus induces a robust antitumor immune response in mice.
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