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Dormant tumor cells interact with memory CD8+ T cells in RET transgenic mouse melanoma model.
Cancer Lett 2020; 474:74-81CL

Abstract

Melanoma is an aggressive form of skin-cancer. Melanoma cells are characterized by their plasticity, resulting in therapy resistance. Using RET transgenic mouse melanoma model, we characterized dormant tumor cells accumulated in the bone marrow (BM) and investigated their interaction with effector memory CD8+ T cells. We found that cells expressing melanoma-associated antigen tyrosinase related protein (TRP)-2 and stemness marker CD133 represented less than 1.5% of all melanoma cells in primary skin lesions and metastatic lymph nodes. The majority of these cells were negative for the proliferation marker Ki67. In the BM, CD133+TRP-2+ melanoma cells displayed an aberrant expression of p16, p27, Ki67 and PCNA proteins, suggesting their dormant phenotype. Moreover, these cells were characterized by an elevated expression of various molecules characterized stemness, metastatic, angiogenic and immunosuppressive properties such as CD271, CD34, HIF-1α, CXCR3, CXCR4, VEGR2, PD-L1, CTLA-4, CD39 and CCR4 as compared to their CD133- counterparts. Disseminated BM dormant TRP-2+ tumor cells were found to be co-localized with memory CD8+ T cells. Our data suggest that these dormant melanoma cells in the BM could play an important role in the maintenance of memory T cells in the BM.

Authors+Show Affiliations

Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany; Faculty of Higher Studies Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany.Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany. Electronic address: v.umansky@dkfz-heidelberg.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31962142

Citation

Flores-Guzmán, Fernando, et al. "Dormant Tumor Cells Interact With Memory CD8+ T Cells in RET Transgenic Mouse Melanoma Model." Cancer Letters, vol. 474, 2020, pp. 74-81.
Flores-Guzmán F, Utikal J, Umansky V. Dormant tumor cells interact with memory CD8+ T cells in RET transgenic mouse melanoma model. Cancer Lett. 2020;474:74-81.
Flores-Guzmán, F., Utikal, J., & Umansky, V. (2020). Dormant tumor cells interact with memory CD8+ T cells in RET transgenic mouse melanoma model. Cancer Letters, 474, pp. 74-81. doi:10.1016/j.canlet.2020.01.016.
Flores-Guzmán F, Utikal J, Umansky V. Dormant Tumor Cells Interact With Memory CD8+ T Cells in RET Transgenic Mouse Melanoma Model. Cancer Lett. 2020 Jan 18;474:74-81. PubMed PMID: 31962142.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dormant tumor cells interact with memory CD8+ T cells in RET transgenic mouse melanoma model. AU - Flores-Guzmán,Fernando, AU - Utikal,Jochen, AU - Umansky,Viktor, Y1 - 2020/01/18/ PY - 2019/11/06/received PY - 2019/12/21/revised PY - 2020/01/15/accepted PY - 2020/1/22/pubmed PY - 2020/1/22/medline PY - 2020/1/22/entrez KW - Immunosuppression KW - Memory T cells KW - Plasticity KW - Tumor dormancy SP - 74 EP - 81 JF - Cancer letters JO - Cancer Lett. VL - 474 N2 - Melanoma is an aggressive form of skin-cancer. Melanoma cells are characterized by their plasticity, resulting in therapy resistance. Using RET transgenic mouse melanoma model, we characterized dormant tumor cells accumulated in the bone marrow (BM) and investigated their interaction with effector memory CD8+ T cells. We found that cells expressing melanoma-associated antigen tyrosinase related protein (TRP)-2 and stemness marker CD133 represented less than 1.5% of all melanoma cells in primary skin lesions and metastatic lymph nodes. The majority of these cells were negative for the proliferation marker Ki67. In the BM, CD133+TRP-2+ melanoma cells displayed an aberrant expression of p16, p27, Ki67 and PCNA proteins, suggesting their dormant phenotype. Moreover, these cells were characterized by an elevated expression of various molecules characterized stemness, metastatic, angiogenic and immunosuppressive properties such as CD271, CD34, HIF-1α, CXCR3, CXCR4, VEGR2, PD-L1, CTLA-4, CD39 and CCR4 as compared to their CD133- counterparts. Disseminated BM dormant TRP-2+ tumor cells were found to be co-localized with memory CD8+ T cells. Our data suggest that these dormant melanoma cells in the BM could play an important role in the maintenance of memory T cells in the BM. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/31962142/Dormant_tumor_cells_interact_with_memory_CD8+_T_cells_in_RET_transgenic_mouse_melanoma_model L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(20)30024-0 DB - PRIME DP - Unbound Medicine ER -