Lipid Signaling Enforces Functional Specialization of Treg Cells in Tumors

Scientists showed that inhibiting lipid synthesis and metabolic signaling that were dependent on sterol-regulatory-element-binding proteins in Treg cells unleashed effective antitumor immune responses without autoimmune toxicity.
[Nature]
Lim, S. A., Wei, J., Nguyen, T.-L. M., Shi, H., Su, W., Palacios, G., Dhungana, Y., Chapman, N. M., Long, L., Saravia, J., Vogel, P., & Chi, H. (2021). Lipid signalling enforces functional specialization of T reg cells in tumours. Nature, 1–6. https://doi.org/10.1038/s41586-021-03235-6 Cite
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Gene Deconvolution Reveals Aberrant Liver Regeneration and Immune Cell Infiltration in Alcohol-Associated Hepatitis

Investigators combined single‐cell RNA‐seq data from healthy livers and peripheral immune cells to measure cell proportions in chronic liver diseases.
[Hepatology]
Kim, A., Wu, X., Allende, D. S., & Nagy, L. E. (n.d.). Gene deconvolution reveals aberrant liver regeneration and immune cell infiltration in alcohol-associated hepatitis. Hepatology, n/a(n/a). https://doi.org/https://doi.org/10.1002/hep.31759 Cite
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Astrocytes Lure CXCR2-Expressing CD4+ T Cells to Gray Matter via TAK1-Mediated Chemokine Production in a Mouse Model of Multiple Sclerosis

Researchers used a modified experimental autoimmune encephalomyelitis mouse model that displayed severe neuronal damage to investigate the interplay between peripheral immune cells and glial cells in the event of neuronal damage.
[Proceedings of the National Academy of Sciences of the United States of America]
Khaw, Y. M., Tierney, A., Cunningham, C., Soto-Díaz, K., Kang, E., Steelman, A. J., & Inoue, M. (2021). Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis. Proceedings of the National Academy of Sciences, 118(8). https://doi.org/10.1073/pnas.2017213118 Cite
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HIF2α is a Direct Regulator of Neutrophil Motility

Scientists revealed that activation of the Hypoxia Inducible Factor-2 (HIF2α) due to deficiency of HIF-prolyl hydroxylase domain protein-2 boosts neutrophil migration specifically through highly confined microenvironments.
[Blood]
Sormendi, S., Deygas, M., Sinha, A., Bernard, M. L. M., Krüger, A., Koutzelis, I., Le Lay, G. M., Sáez, P. J., Gerlach, M., Franke, K., Meneses, A., Kräter, M., Palladini, A., Guck, J., Coskun, Ü., Chavakis, T., Vargas, P., & Wielockx, B. (2021). HIF2α is a Direct Regulator of Neutrophil Motility. Blood, blood.2020007505. https://doi.org/10.1182/blood.2020007505 Cite
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Microbiota‐Driven Activation of Intrahepatic B Cells Aggravates Nonalcoholic Steatohepatitis through Innate and Adaptive Signaling

Scientists report that nonalcoholic steatohepatitis livers accumulate B cells with elevated pro‐inflammatory cytokine secretion and antigen‐presentation ability.
[Hepatology]
Barrow, F., Khan, S., Fredrickson, G., Wang, H., Dietsche, K., Parthiban, P., Robert, S., Kaiser, T., Winer, S., Herman, A., Adeyi, O., Mouzaki, M., Khoruts, A., Hogquist, K. A., Staley, C., Winer, D. A., & Revelo, X. S. (n.d.). Microbiota-Driven Activation of Intrahepatic B Cells Aggravates Nonalcoholic Steatohepatitis through Innate and Adaptive Signaling. Hepatology, n/a(n/a). https://doi.org/https://doi.org/10.1002/hep.31755 Cite
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Continuous Human Uterine NK Cell Differentiation in Response to Endometrial Regeneration and Pregnancy

By surface proteome and transcriptome analysis as well as using humanized mice, researchers identified a differentiation pathway of uterine natural killer cells in vitro and in vivo with sequential acquisition of killer cell immunoglobulin-like receptors and CD39.
[Science Immunology]
Strunz, B., Bister, J., Jönsson, H., Filipovic, I., Crona-Guterstam, Y., Kvedaraite, E., Sleiers, N., Dumitrescu, B., Brännström, M., Lentini, A., Reinius, B., Cornillet, M., Willinger, T., Gidlöf, S., Hamilton, R. S., Ivarsson, M. A., & Björkström, N. K. (2021). Continuous human uterine NK cell differentiation in response to endometrial regeneration and pregnancy. Science Immunology, 6(56). https://doi.org/10.1126/sciimmunol.abb7800 Cite
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Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8+ T Cells

Researchers found that tumor-infiltrating CD8+ T cells initially expressed CD49b, gained CD49a, and then lost CD49b over the course of tumor outgrowth.
[Cancer Immunology Research]
Melssen, M. M., Lindsay, R. S., Stasiak, K., Rodriguez, A. B., Briegel, A. M., Cyranowski, S., Rutkowski, M. R., Conaway, M. R., Melief, C. J., Burg, S. H. van der, Eyo, U., Slingluff, C. L., & Engelhard, V. H. (2021). Differential expression of CD49a and CD49b determines localization and function of tumor-infiltrating CD8+ T cells. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0427 Cite
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EBF1 and PAX5 Control Pro-B Cell Expansion via Opposing Regulation of the Myc Gene

Researchers report that impaired Early B cell Factor 1 (EBF1) function in mouse B-cell progenitors resulted in reduced expression of Myc.
[Blood]
Somasundaram, R., Jensen, C. T., Tingvall-Gustafsson, J., Åhsberg, J., Okuyama, K., Prasad, M., Hagman, J., Wang, X., Soneji, S., Strid, T., Ungerbäck, J., & Sigvardsson, M. (2021). EBF1 and PAX5 control pro-B cell expansion via opposing regulation of the Myc gene. Blood, blood.2020009564. https://doi.org/10.1182/blood.2020009564 Cite
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5-Fluorouracil Efficacy Requires Anti-tumor Immunity Triggered by Cancer-Cell-Intrinsic STING

Through modeling 5‐FU response of murine colon and melanoma tumors, the authors report that effective reduction of tumor burden by 5‐FU was dependent on anti‐tumor immunity triggered by the activation of cancer‐cell‐intrinsic STING.
[EMBO Journal]
Tian, J., Zhang, D., Kurbatov, V., Wang, Q., Wang, Y., Fang, D., Wu, L., Bosenberg, M., Muzumdar, M. D., Khan, S., Lu, Q., Yan, Q., & Lu, J. (2021). 5-Fluorouracil efficacy requires anti-tumor immunity triggered by cancer-cell-intrinsic STING. The EMBO Journal, n/a(n/a), e106065. https://doi.org/10.15252/embj.2020106065 Cite
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DGKA Mediates Resistance to PD-1 Blockade

Scientists demonstrated that diacylglycerol kinase alpha (Dgka) mediated T-cell dysfunction during anti-PD-1 therapy by exacerbating the exhaustion of reinvigorated tumor-specific T cells.
[Cancer Immunology Research]
Fu, L., Li, S., Xiao, W., Yu, K., Li, S., Yuan, S., Shen, J., Dong, X., Fang, Z., Zhang, J., Chen, S., Li, W., You, H., Xia, X., Kang, T., Tan, J., Chen, G., Yang, A.-K., Gao, Y., & Zhou, P. (2021). DGKA Mediates Resistance to PD-1 Blockade. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0216 Cite
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Protein-Based Immune Profiles of Basal-Like vs. Luminal Breast Cancers

In epithelium-enriched areas, immune signals were also detectable and varied by subtype, with regulatory T-cell markers being higher in Basal-like vs. Luminal breast cancer.
[Laboratory Investigation]
Walens, A., Olsson, L. T., Gao, X., Hamilton, A. M., Kirk, E. L., Cohen, S. M., Midkiff, B. R., Xia, Y., Sherman, M. E., Nikolaishvili-Feinberg, N., Serody, J. S., Hoadley, K. A., Troester, M. A., & Calhoun, B. C. (2021). Protein-based immune profiles of basal-like vs. luminal breast cancers. Laboratory Investigation, 1–9. https://doi.org/10.1038/s41374-020-00506-0 Cite
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