Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0278883 (
metastatic melanoma
)
6,224
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although remission rates for
metastatic melanoma
are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13,
CCL19
, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24). Furthermore, any of the 4 parameters (prevalidated gene expression signature, TILs, CD3, and in particular MI) improved the ability of Tumor, Node, Metastasis (TNM) staging to predict postrecurrence survival; MI was the most significant contributor (HR = 2.13, P = 0.0008). An immune response gene expression signature and presence of TILs and CD3+ cells signify immune surveillance as a mechanism for prolonged survival in these patients and indicate improved patient subcategorization beyond current TNM staging.
...
PMID:Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival. 2030 34
Immune checkpoint blockade therapy has changed prognoses for many melanoma patients. However, immune responses that correlate with clinical progression of the disease are still poorly understood. To identify immune responses correlating with melanoma clinical evolution, we analyzed serum cytokines as well as circulating NK and T-cell subpopulations from melanoma patients. The patients' immune profiles suggested that melanoma progression leads to changes in peripheral blood NK and T-cell subsets. Stage IV melanoma was characterized by an increased frequency of CCR7
+
CD56
bright
NK cells as well as high serum concentrations of the CCR7 ligand
CCL19
. CCR7 expression and
CCL19
secretion were also observed in melanoma cell lines. The CCR7
+
melanoma cell subpopulation coexpressed PD-L1 and Galectin-9 and had stemness properties. Analysis of melanoma-derived cancer stem cells (CSC) showed high CCR7 expression; these CSCs were efficiently recognized and killed by NK cells. An accumulation of CCR7
+
, PD-L1
+
, and Galectin-9
+
melanoma cells in melanoma metastases was demonstrated
ex vivo
Altogether, our data identify biomarkers that may mark a CCR7-driven
metastatic melanoma
pathway.
...
PMID:Accumulation of Circulating CCR7
+
Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway. 3094 Jun 44
