Reversal of Pre-existing NGFR-Driven Tumor and Immune Therapy Resistance

Researchers chronically exposed patient-derived melanoma cell lines to differentiation antigen-specific cytotoxic T cells and observed strong enrichment of a pre-existing NGFRhi population.
[Nature Communications]
Boshuizen, J., Vredevoogd, D. W., Krijgsman, O., Ligtenberg, M. A., Blankenstein, S., de Bruijn, B., Frederick, D. T., Kenski, J. C. N., Parren, M., Brüggemann, M., Madu, M. F., Rozeman, E. A., Song, J.-Y., Horlings, H. M., Blank, C. U., van Akkooi, A. C. J., Flaherty, K. T., Boland, G. M., & Peeper, D. S. (2020). Reversal of pre-existing NGFR-driven tumor and immune therapy resistance. Nature Communications, 11(1), 3946. https://doi.org/10.1038/s41467-020-17739-8 Cite
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Amyloid Aggregates Accumulate in Melanoma Metastasis Modulating YAP Activity

Using secretome analyses, the authors revealed the extracellular accumulation of amyloidogenic proteins, i.e. premelanosome protein, in metastatic melanoma, together with proteins that assist amyloid maturation into fibrils.
[EMBO Reports]
Matafora, V., Farris, F., Restuccia, U., Tamburri, S., Martano, G., Bernardelli, C., Sofia, A., Pisati, F., Casagrande, F., Lazzari, L., Marsoni, S., Bonoldi, E., & Bachi, A. (2020). Amyloid aggregates accumulate in melanoma metastasis modulating YAP activity. EMBO Reports, n/a(n/a), e50446. https://doi.org/10.15252/embr.202050446 Cite
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Adoptive T Cell Therapy Targeting Different Gene Products Reveals Diverse and Context-Dependent Immune Evasion in Melanoma

Researchers examined how regulation and function of gene products that provide the target epitopes for CD8+ T cell anti-tumor immunity influence therapeutic efficacy and resistance.
[Immunity]
Effern, M., Glodde, N., Braun, M., Liebing, J., Boll, H. N., Yong, M., Bawden, E., Hinze, D., Boorn-Konijnenberg, D. van den, Daoud, M., Aymans, P., Landsberg, J., Smyth, M. J., Flatz, L., Tüting, T., Bald, T., Gebhardt, T., & Hölzel, M. (2020). Adoptive T Cell Therapy Targeting Different Gene Products Reveals Diverse and Context-Dependent Immune Evasion in Melanoma. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.07.007 Cite
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Correlative Study of Epigenetic Regulation of Tumor Microenvironment in Spindle Cell Melanomas and Cutaneous Malignant Peripheral Nerve Sheath Tumors

Scientists investigated the epigenetic regulation of promoters and gene bodies and their effect on the tumor microenvironment composition of cutaneous malignant peripheral nerve sheath tumors and spindle cell melanomas.
[Scientific Reports]
Vougiouklakis, T., Aung, P. P., Vasudevaraja, V., Prieto, V. G., Torres-Cabala, C. A., Sulman, E. P., Snuderl, M., & Jour, G. (2020). Correlative study of epigenetic regulation of tumor microenvironment in spindle cell melanomas and cutaneous malignant peripheral nerve sheath tumors. Scientific Reports, 10(1), 12996. https://doi.org/10.1038/s41598-020-69787-1 Cite
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Adoptive T Cell Therapy Targeting Different Gene Products Reveals Diverse and Context-Dependent Immune Evasion in Melanoma

Targeting melanosomal proteins or oncogenic CDK4R24C by adoptive cell transfer of the same epitope-specific CD8+ T cells revealed diverse genetic and non-genetic immune escape mechanisms.
[Immunity]
Effern, M., Glodde, N., Braun, M., Liebing, J., Boll, H. N., Yong, M., Bawden, E., Hinze, D., Boorn-Konijnenberg, D. van den, Daoud, M., Aymans, P., Landsberg, J., Smyth, M. J., Flatz, L., Tüting, T., Bald, T., Gebhardt, T., & Hölzel, M. (2020). Adoptive T Cell Therapy Targeting Different Gene Products Reveals Diverse and Context-Dependent Immune Evasion in Melanoma. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.07.007 Cite
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Fine-Needle Aspiration-Based Patient-Derived Cancer Organoids

Researchers presented a simple and minimally invasive fine-needle aspiration-based organoid culture technique using a variety of tumor types including gastrointestinal, thyroid, melanoma, and kidney.
[iScience]
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Signaling of Tumor-Derived sEV Impacts Melanoma Progression

The authors feature melanoma cell-derived exosomes with special emphasis on exosome-mediated signaling between melanoma cells and the host immune system.
[International Journal of Molecular Sciences]
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Checkmate Pharmaceuticals Granted FDA Fast Track Designation for CMP-001 Combined with PD-1 Blockade in the Treatment of Certain Types of Metastatic or Unresectable Melanoma

Checkmate Pharmaceuticals, Inc. announced that the FDA granted Fast Track designation to its product candidate, CMP-001, in combination with a programmed death receptor 1 (PD-1) blocking antibody for initial treatment of patients with unresectable stage III or stage IV melanoma; and treatment of patients with unresectable or metastatic melanoma refractory to prior anti-PD-1 blockade.
[Checkmate Pharmaceuticals (BusinessWire, Inc.)]
Press Release

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Inactivating p53 Is Essential for Nerve Growth Factor Receptor to Promote Melanoma-Initiating Cell-Stemmed Tumorigenesis

Researchers report that a feedback inhibition of p53 by nerve growth factor receptor played an essential role in maintaining the sphere formation and proliferation of melanoma-initiating cells (MICs), and in promoting MIC-derived melanoma growth in vivo.
[Cell Death & Disease]
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Inactivating p53 Is Essential for Nerve Growth Factor Receptor to Promote Melanoma-Initiating Cell-Stemmed Tumorigenesis

Knockdown of nerve growth factor receptor (NGFR) markedly reduced the size and number of spheroid formation of melanoma cells, which could be rescued by ectopically expressed NGFR.
[Cell Death & Disease]
Jiang, L., Huang, S., Wang, J., Zhang, Y., Xiong, Y., Zeng, S. X., & Lu, H. (2020). Inactivating p53 is essential for nerve growth factor receptor to promote melanoma-initiating cell-stemmed tumorigenesis. Cell Death & Disease, 11(7), 1–12. https://doi.org/10.1038/s41419-020-02758-6 Cite
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Oral Exposure to BDE-209 Modulates Metastatic Spread of Melanoma in C57BL/6 Mice Inoculated with B16-F10 Cells

In vitro studies showed that decabromodiphenyl ether interfered with murine melanoma cells, modulating cell death rates, proliferation and migration, important events for cancer progression.
[Chemosphere]
Brito, P. M., Biscaia, S. M. P., de Souza, T. L., Ramos, A. B., Leão-Buchir, J., de Almeida Roque, A., de Lima Bellan, D., da Silva Trindade, E., Filipak Neto, F., & de Oliveira Ribeiro, C. A. (2020). Oral exposure to BDE-209 modulates metastatic spread of melanoma in C57BL/6 mice inoculated with B16–F10 cells. Chemosphere, 260, 127556. https://doi.org/10.1016/j.chemosphere.2020.127556 Cite
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IDEAYA Announces IDE196 Program Update and Clinical Protocol Criteria Met for Cohort Expansion in Skin Melanoma for Phase 2 GNAQ/11 Basket Trial

IDEAYA Biosciences, Inc. announced that it has met the clinical protocol criteria for cohort expansion in the cutaneous melanoma cohort of its Phase II basket arm evaluating IDE196 monotherapy in solid tumors harboring GNAQ or GNA11 hotspot mutations (GNAQ/11).
[IDEAYA]
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