Fig. 3 | Nature Communications

Fig. 3

From: LinCCR2+ hematopoietic stem and progenitor cells overcome resistance to PD-1 blockade

Fig. 3

CCR2+HSCs increase T-cell activation within tumor after adoptive cell therapy. a Lineage negative HSCs were further isolated into stem and progenitor cell populations: Sca1 + HSCs, cKit + HSCs, CD133 + HSCs, CD38 + HSCs, CCR2+HSCs. Each progenitor cell population was transferred with tumor-reactive T-cells (generated from GREAT mice) into tumor-bearing mice. Relative amounts of YFP+ was measured in the tumors. b Late-stage tumor-bearing mice received adoptive T-cell therapy and dendritic cell (DC) vaccine with or without HSC transfer. Twenty-one days post transfer, brains were excised and sliced into sections, then analyzed for YFP+ cells within the tumor microenvironment by measuring relative MFI across brain sections (*p = 0.0110, n = 5/group, Mann–Whitney test). c Late-stage tumor-bearing mice received adoptive T-cell therapy and DC vaccine with or without HSC transfer. Draining lymph nodes were harvested and YFP+ CD3+ cells were enumerated to determine the relative amounts of activated T cells, *p = 0.0002, n = 5/group, Mann–Whitney test). d Two groups of KR158 glioma-bearing mice received adoptive T-cell therapy with concomitant transfer of either CCR2HSCs or CCR2+HSCs. Tumors were excised and relative amounts of YFP+ of CD3+ cells were measured with flow cytometry (*p = 0.0002, n = 5/group, unpaired t-test). e Tumor bearing mice were treated with either CCR2+HSC + PD-1 or CCR2HSC + PD-1. Tumors were excised and RNA was isolated to conduct RT2 PCR Array for T- and B-cell activation (Qiagen). Genes represented demonstrated >2-fold change in expression (this has been replicated twice). All error bars represent s.e.m.

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