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Chitinase-3-like 1 protein complexes modulate macrophage-mediated immune suppression in glioblastoma
Apeng Chen, Yinan Jiang, Zhengwei Li, Lingxiang Wu, Ulises Santiago, Han Zou, Chunhui Cai, Vaibhav Sharma, Yongchang Guan, Lauren H. McCarl, Jie Ma, Yijen L. Wu, Joshua Michel, Yi Shi, Liza Konnikova, Nduka M. Amankulor, Pascal O. Zinn, Gary Kohanbash, Sameer Agnihotri, Songjian Lu, Xinghua Lu, Dandan Sun, George K. Gittes, Qianghu Wang, Xiangwei Xiao, Dean Yimlamai, Ian F. Pollack, Carlos J. Camacho, Baoli Hu
Apeng Chen, Yinan Jiang, Zhengwei Li, Lingxiang Wu, Ulises Santiago, Han Zou, Chunhui Cai, Vaibhav Sharma, Yongchang Guan, Lauren H. McCarl, Jie Ma, Yijen L. Wu, Joshua Michel, Yi Shi, Liza Konnikova, Nduka M. Amankulor, Pascal O. Zinn, Gary Kohanbash, Sameer Agnihotri, Songjian Lu, Xinghua Lu, Dandan Sun, George K. Gittes, Qianghu Wang, Xiangwei Xiao, Dean Yimlamai, Ian F. Pollack, Carlos J. Camacho, Baoli Hu
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Research Article Oncology

Chitinase-3-like 1 protein complexes modulate macrophage-mediated immune suppression in glioblastoma

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Abstract

Authors

Apeng Chen, Yinan Jiang, Zhengwei Li, Lingxiang Wu, Ulises Santiago, Han Zou, Chunhui Cai, Vaibhav Sharma, Yongchang Guan, Lauren H. McCarl, Jie Ma, Yijen L. Wu, Joshua Michel, Yi Shi, Liza Konnikova, Nduka M. Amankulor, Pascal O. Zinn, Gary Kohanbash, Sameer Agnihotri, Songjian Lu, Xinghua Lu, Dandan Sun, George K. Gittes, Qianghu Wang, Xiangwei Xiao, Dean Yimlamai, Ian F. Pollack, Carlos J. Camacho, Baoli Hu

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Figure 8

CHI3L1 protein complexes regulate MDM reprogramming in immune suppression and stimulation.

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CHI3L1 protein complexes regulate MDM reprogramming in immune suppressio...
(A) Enrichment of top 10 GO biological pathways in TAMs derived from C57BL/6 mice bearing QPP7 with shChi3l1 compared with shSC. (B) Flow cytometry analysis showing active CD4+ and CD8+ cells in GL261 tumors with CHI3L1 OE compared with vector controls. (C) Flow cytometry analysis showing active CD4+ and CD8+ cells in QPP7 tumors with Chi3l1 KD compared with shSC. Depletion antibodies against CD4 and CD8 (10 mg/kg) were injected intraperitoneally every 3 days for a total of 8 times after tumor implantation. Kaplan-Meier tumor-free survival analysis of mice bearing GL261 overexpressing CHI3L1 (D) and mice bearing QPP7 with Chi3l1 KD (F). Flow cytometry analysis showing CD4+ and CD8+ cell populations within the tumors from GL261 models (E) and QPP7 models (G) with antibody depletion. Each dot represents 1 mouse; data are presented as mean ± SEM. P values were calculated using a 1-tailed, unpaired t test. (H) qRT-PCR for indicated gene expression in M0 BMDMs treated with rCHI3L1 (2.5 μg/mL), rGal3 (2.5 μg/mL), rGal3BP (5.0 μg/mL), and combinations for 24 hours. Data are presented as mean ± SEM from at least 2 independent experiments. P values were calculated using 1-way ANOVA with Tukey’s multiple comparisons test. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001. (I–K) IB analysis of indicated protein levels in M0 BMDMs treated with rCHI3L1 (2.5 μg/mL), rGal3 (2.5 μg/mL), rGal3BP (5.0 μg/mL), and combinations for 30 minutes or 4 hours (p-p65 and p65). (L) GSEA plots depicting mTOR1 and TNFA/NFKB signaling pathways in TAMs derived from C57BL/6 mice bearing QPP7 with shChi3l1 compared with shSC. NES, normalized enrichment score.

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