Hematopoiesis: A Layered Organization across Species

The authors evaluate evidence for a layered hematopoietic system across species. They discuss mechanisms and selective pressures leading to the temporal generation of different cell types.
[Frontiers in Cell and Developmental Biology]
Elsaid, R., Soares-Da-Silva, F., Peixoto, M., Amiri, D., Mackowski, N., Pereira, P., Bandeira, A., & Cumano, An. (2020). Hematopoiesis: a layered organization across species. Frontiers in Cell and Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.606642 Cite
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Senescent Cells Promote Tissue NAD+ Decline during Aging via the Activation of CD38+ Macrophages

Researchers showed that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation.
[Nature Metabolism]
Senescent cells promote tissue NAD + decline during ageing via the activation of CD38 + macrophages | Nature Metabolism. (n.d.). Retrieved November 19, 2020, from https://www.nature.com/articles/s42255-020-00305-3 Cite
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Skeletal Muscle Healing by M1-Like Macrophages Produced by Transient Expression of Exogenous GM-CSF

Increasing the number of M1-like macrophages immediately after traumatic muscle injury promoted muscle recovery with less fibrosis, and this can be achieved by the transient expression of granulocyte and monocyte colony stimulating factor (GM-CSF).
[Stem Cell Research & Therapy]
Martins, L., Gallo, C. C., Honda, T. S. B., Alves, P. T., Stilhano, R. S., Rosa, D. S., Koh, T. J., & Han, S. W. (2020). Skeletal muscle healing by M1-like macrophages produced by transient expression of exogenous GM-CSF. Stem Cell Research & Therapy, 11(1), 473. https://doi.org/10.1186/s13287-020-01992-1 Cite
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Jounce Therapeutics Receives Study May Proceed Letter from US FDA to Initiate Phase I Clinical Trial of JTX-8064 Targeting the LILRB2/ILT4 Mechanism

Jounce Therapeutics, Inc. have received a Study May Proceed Letter from the US FDA to begin a Phase I trial, named INNATE, for JTX-8064. JTX-8064 is an anti-Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) antibody and is the first tumor-associated macrophage candidate from Jounce’s Translational Science Platform. The INNATE trial represents the first time two wholly owned Jounce immunotherapies are combined to target two different immune cells in the tumor microenvironment.
[Jounce Therapeutics, Inc.]
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S100 Calcium-Binding Protein A9 from Tumor-Associated Macrophage Enhances Cancer Stem Cell-Like Properties of Hepatocellular Carcinoma

S100A9 expression in tumor tissues was associated with poor survival of hepatocellular carcinoma patients. It could enhance the stem cell‐like properties of HepG2 and MHCC‐97H cells by activating nuclear factor‐kappa B signaling pathway through advanced glycosylation end product‐specific receptor in a Ca2+‐dependent manner.
[International Journal of Cancer]
Wei, R., Zhu, W.-W., Yu, G.-Y., Wang, X., Gao, C., Zhou, X., Lin, Z.-F., Shao, W.-Q., Wang, S.-H., Lu, M., & Qin, L.-X. (n.d.). S100 calcium-binding protein A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma. International Journal of Cancer, n/a(n/a). https://doi.org/https://doi.org/10.1002/ijc.33371 Cite
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Bone Marrow Adipogenic Lineage Precursors (MALPs) Promote Osteoclastogenesis in Bone Remodeling and Pathologic Bone Loss

Scientists demonstrated that mice with RANKL deficiency in marrow adipogenic lineage precursors MALPs have a drastic increase in trabecular bone mass in long bones and vertebrae starting from one month of age, while their cortical bone appears normal.
[Journal of Clinical Investigation]
Yu, W., Zhong, L., Yao, L., Wei, Y., Gui, T., Li, Z., Kim, H., Holdreith, N., Jiang, X., Tong, W., Dyment, N. A., Liu, X. S., Yang, S., Choi, Y., Ahn, J., & Qin, L. (2020). Bone marrow adipogenic lineage precursors (MALPs) promote osteoclastogenesis in bone remodeling and pathologic bone loss. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI140214 Cite
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Tumor Necrosis Factor α Inhibition Overcomes Immunosuppressive M2b Macrophage-Induced Bevacizumab Resistance in Triple-Negative Breast Cancer

Scientists developed a TNBC model resistant to bevacizumab under bevacizumab continuous administration. It was found that proportion of a specific subset of tumor-associated macrophages characterized as M2b increased and responsible for acquired resistance to bevacizumab.
[Cell Death & Disease]
Tumor necrosis factor α inhibition overcomes immunosuppressive M2b macrophage-induced bevacizumab resistance in triple-negative breast cancer | Cell Death & Disease. (n.d.). Retrieved November 19, 2020, from https://www.nature.com/articles/s41419-020-03161-x Cite
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Mutations in BRCA1 and BRCA2 Differentially Affect the Tumor Microenvironment and Response to Checkpoint Blockade Immunotherapy

Investigators report differential effects of mutations in the homologous recombination genes BRCA1 and BRCA2 on response to ICB in mouse and human tumors.
[Nature Cancer]
Samstein, R. M., Krishna, C., Ma, X., Pei, X., Lee, K.-W., Makarov, V., Kuo, F., Chung, J., Srivastava, R. M., Purohit, T. A., Hoen, D. R., Mandal, R., Setton, J., Wu, W., Shah, R., Qeriqi, B., Chang, Q., Kendall, S., Braunstein, L., … Riaz, N. (2020). Mutations in BRCA1 and BRCA2 differentially affect the tumor microenvironment and response to checkpoint blockade immunotherapy. Nature Cancer, 1–16. https://doi.org/10.1038/s43018-020-00139-8 Cite
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CSF1R Inhibition Depletes Tumor-Associated Macrophages and Attenuates Tumor Progression in a Mouse Sonic Hedgehog-Medulloblastoma Model

By combining longitudinal manganese-enhanced magnetic resonance imaging and immune profiling of a sporadic mouse model of SHH-MB, researchers found the density of TAMs was higher in the ~50% of tumors that progress to lethal disease.
[Oncogene]
CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic Hedgehog-Medulloblastoma model | Oncogene. (n.d.). Retrieved November 7, 2020, from https://www.nature.com/articles/s41388-020-01536-0 Cite
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The SUMOylation of TAB2 Mediated by TRIM60 Inhibits MAPK/NF-κB Activation and the Innate Immune Response

Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation, accompanied by elevated levels of proinflammatory cytokines but not IFN-I.
[Cellular & Molecular Immunology]
Gu, Z., Chen, X., Yang, W., Qi, Y., Yu, H., Wang, X., Gong, Y., Chen, Q., Zhong, B., Dai, L., Qi, S., Zhang, Z., Zhang, H., & Hu, H. (2020). The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response. Cellular & Molecular Immunology, 1–14. https://doi.org/10.1038/s41423-020-00564-w Cite
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Characterisation of CD4+ T-Cell Subtypes Using Single Cell RNA Sequencing and the Impact of Cell Number and Sequencing Depth

Scientists found that the reparative macrophage transition was dictated by B-cell adapter for PI3K (BCAP). Mice harboring a macrophage-specific deletion of BCAP fail to recover from and succumb to dextran sulfate sodium-induced colitis due to prolonged intestinal inflammation and impaired tissue repair.
[Proceedings of the National Academy of Sciences of the United States of America]
Characterisation of CD4+ T-cell subtypes using single cell RNA sequencing and the impact of cell number and sequencing depth | Scientific Reports. (n.d.). Retrieved November 17, 2020, from https://www.nature.com/articles/s41598-020-76972-9 Cite
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