Midkine Rewires the Melanoma Microenvironment Toward a Tolerogenic and Immune-Resistant State

Midkine was found to control the transcriptome of melanoma cells, allowing for coordinated activation of nuclear factor-κB and downregulation of interferon-associated pathways.
[Nature Medicine]
Cerezo-Wallis, D., Contreras-Alcalde, M., Troulé, K., Catena, X., Mucientes, C., Calvo, T. G., Cañón, E., Tejedo, C., Pennacchi, P. C., Hogan, S., Kölblinger, P., Tejero, H., Chen, A. X., Ibarz, N., Graña-Castro, O., Martinez, L., Muñoz, J., Ortiz-Romero, P., Rodriguez-Peralto, J. L., … Soengas, M. S. (2020). Midkine rewires the melanoma microenvironment toward a tolerogenic and immune-resistant state. Nature Medicine, 1–13. https://doi.org/10.1038/s41591-020-1073-3 Cite
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Uncoupling Interferon Signaling and Antigen Presentation to Overcome Immunotherapy Resistance Due to JAK1 Loss in Melanoma

Investigators generated models of interferon signaling defects in B16 murine melanoma observed in patients with acquired resistance to immune checkpoint blockade.
[Science Translational Medicine]
Kalbasi, A., Tariveranmoshabad, M., Hakimi, K., Kremer, S., Campbell, K. M., Funes, J. M., Vega-Crespo, A., Parisi, G., Champekar, A., Nguyen, C., Torrejon, D., Shin, D., Zaretsky, J. M., Damoiseaux, R. D., Speiser, D. E., Lopez-Casas, P. P., Quintero, M., & Ribas, A. (2020). Uncoupling interferon signaling and antigen presentation to overcome immunotherapy resistance due to JAK1 loss in melanoma. Science Translational Medicine, 12(565). https://doi.org/10.1126/scitranslmed.abb0152 Cite
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Genome-Wide RNAi Screen for Genes Regulating Glycolytic Response to Vemurafenib in BRAFV600

Scientists presented a multiparameter genome-wide siRNA screening dataset of genes that when depleted, improved the viability and glycolytic response to vemurafenib in BRAFV600 mutated melanoma cells.
[Scientific Data]
Smith, L. K., Parmenter, T., Gould, C. M., Madhamshettiwar, P. B., Sheppard, K. E., Simpson, K. J., & McArthur, G. A. (2020). Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAF V600 melanoma cells. Scientific Data, 7(1), 339. https://doi.org/10.1038/s41597-020-00683-z Cite
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The Amino-Terminal Oligomerization Domain of Angiopoietin-2 Affects Vascular Remodeling, Mammary Gland Tumor Growth, and Lung Metastasis in Mice

Scientists used a knock-in mouse line, a genetic model for breast cancer and metastasis, a syngeneic melanoma lung colonization model, and orthotopic injection of E0771 breast cancer cells to show that alternative forms increased the diversity of Angiopoietin-2 function.
[Cancer Research]
Kapiainen, E., Kihlström, M. K., Pietilä, R., Kaakinen, M., Ronkainen, V.-P., Tu, H., Heikkinen, A., Devarajan, R., Miinalainen, I., Laitakari, A., Ansarizadeh, M., Zhang, Q., Wei, G.-H., Ruddock, L., Pihlajaniemi, T., Elamaa, H., & Eklund, L. (2020). The amino-terminal oligomerization domain of Angiopoietin-2 affects vascular remodeling, mammary gland tumor growth, and lung metastasis in mice. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-19-1904 Cite
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Nicotinamide Inhibits Melanoma In Vitro and In Vivo

The anti-melanoma activity of Nicotinamide, the amide form of Niacin, was assessed in vitro and in vivo.
[Journal of Experimental & Clinical Cancer Research]
Scatozza, F., Moschella, F., D’Arcangelo, D., Rossi, S., Tabolacci, C., Giampietri, C., Proietti, E., Facchiano, F., & Facchiano, A. (2020). Nicotinamide inhibits melanoma in vitro and in vivo. Journal of Experimental & Clinical Cancer Research, 39(1), 211. https://doi.org/10.1186/s13046-020-01719-3 Cite
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Mutant SF3B1 Promotes AKT and NF-kB Driven Mammary Tumorigenesis

Scientists identified that SF3B1 mutations in mammary epithelial and breast cancer cells induced a recurrent pattern of aberrant splicing leading to activation of AKT and NF-kB, enhanced cell migration, and accelerated tumorigenesis.
[Journal of Clinical Investigation]
Liu, B., Liu, Z., Chen, S., Ki, M., Erickson, C., Reis-Filho, J. S., Durham, B. H., Chang, Q., Stanchina, E. de, Sun, Y., Rabadan, R., Abdel-Wahab, O., & Chandarlapaty, S. (2020). Mutant SF3B1 promotes AKT and NF-kB driven mammary tumorigenesis. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI138315 Cite
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A Gene Expression Signature of TREM2hi Macrophages and γδ T Cells Predicts Immunotherapy Response

Researchers re-analyzed a publicly available single-cell RNA sequencing dataset of melanoma samples of patients subjected to immune checkpoint therapy and identified a subset of macrophages overexpressing TREM2 and a subset of gammadelta T cells that were both overrepresented in the non-responding tumors.
[Nature Communications]
Xiong, D., Wang, Y., & You, M. (2020). A gene expression signature of TREM2 hi macrophages and γδ T cells predicts immunotherapy response. Nature Communications, 11(1), 5084. https://doi.org/10.1038/s41467-020-18546-x Cite
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Tim-3 Promotes Tube Formation and Decreases Tight Junction Formation in Vascular Endothelial Cells

Tim-3 was overexpressed in vascular endothelial HMVECs and HUVECs and in vitro assays were used to determine that Tim-3 promoted cell proliferation, migration, invasion and tube formation through activating cyclin D1, Ras homolog gene family member A and vascular endothelial growth factor receptor 2.
[Bioscience Reports]
Cong, Y., Wang, X., Wang, S., Qiao, G., Li, Y., Cao, J., Jiang, W. G., & Cui, Y. (n.d.). Tim-3 promotes tube formation and decreases tight junction formation in vascular endothelial cells. Bioscience Reports. https://doi.org/10.1042/BSR20202130 Cite
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The Genomic Landscapes of Individual Melanocytes from Human Skin

Scientists described ways to overcome obstacles in the context of normal human skin, thus offering a glimpse into the genomic landscapes of individual melanocytes from human skin.
[Nature]
Tang, J., Fewings, E., Chang, D., Zeng, H., Liu, S., Jorapur, A., Belote, R. L., McNeal, A. S., Tan, T. M., Yeh, I., Arron, S. T., Judson-Torres, R. L., Bastian, B. C., & Shain, A. H. (2020). The genomic landscapes of individual melanocytes from human skin. Nature, 1–6. https://doi.org/10.1038/s41586-020-2785-8 Cite
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Fructose Promotes Cytoprotection in Melanoma Tumors and Resistance to Immunotherapy

An increase in heme oxygenase-1 protein was recapitulated in human A375 melanoma cells exposed to fructose in culture.
[Cancer Immunology Research]
Kuehm, L. M., Khojandi, N., Piening, A., Klevorn, L. E., Geraud, S. C., McLaughlin, N. R., Griffett, K., Burris, T. P., Pyles, K. D., Nelson, A. M., Preuss, M. L., Bockerstett, K. A., Donlin, M. J., McCommis, K. S., DiPaolo, R. J., & Teague, R. M. (2020). Fructose promotes cytoprotection in melanoma tumors and resistance to immunotherapy. Cancer Immunology Research. https://doi.org/10.1158/2326-6066.CIR-20-0396 Cite
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HIF-2α Is Indispensable for Regulatory T Cell Function

Researchers showed that Treg cell development was normal in mice with Foxp3-specific knockout of hypoxia-inducible factor 1α (HIF-1α) or HIF-2α.
[Nature Communications]
Hsu, T.-S., Lin, Y.-L., Wang, Y.-A., Mo, S.-T., Chi, P.-Y., Lai, A. C.-Y., Pan, H.-Y., Chang, Y.-J., & Lai, M.-Z. (2020). HIF-2α is indispensable for regulatory T cell function. Nature Communications, 11(1), 5005. https://doi.org/10.1038/s41467-020-18731-y Cite
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