Page 16 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Single-cell RNA-seq in malignant skin tumors

for clinical prognosis and predicting immune therapy impacts on melanoma patients. Compared to the other
response in melanoma patients. The role of fibroblasts in two phenotypes, patients with the “immune hot/active”
melanoma is complex. Lian et al. found that fibroblasts phenotype, characterized by more non-regulated B-cells,
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promote melanoma cell proliferation and metastasis, with cytotoxic CD8 T-cells, and lower mixed states CD8 T-cells,
+
+
CEMIP and NKD1 fibroblast clusters in CM closely tend to respond better to anti-PD1 treatment. In summary,
associated with resistance to immunotherapy. Another single-cell sequencing plays a crucial role in gaining a
study on heterospheroids in CM revealed that fibroblast deeper understanding of the immune microenvironment,
clusters could be differentiated based on their impact on discovering new immunotherapy targets, and optimizing
cancer cells. The pro-inflammatory cytokine interleukin-6 immunotherapy strategies, ultimately improving the
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significantly enhanced melanoma invasion, providing clinical efficacy of immunotherapy.
insights into the development of CM. In summary, single-
cell analysis provides a high-resolution tool for an in-depth 5.4. Single-cell technology facilitates research on
exploration of melanoma heterogeneity, aiding in the treatment resistance mechanisms in CM
formulation of more effective treatment strategies and Research on the mechanisms of treatment resistance in CM
improving treatment success rates. is crucial. Patients with BRAF mutations often receive
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treatment with BRAF inhibitors such as vemurafenib
5.3. Single-cell identification of the immune and dabrafenib. However, resistance tends to develop
microenvironment to guide immunotherapy in the later stages of treatment, potentially involving
The TME refers to the local tissue and the area abnormalities in multiple signaling pathways, including
surrounding tumor cells, playing a crucial regulatory role the MAPK pathway. Immunotherapy, especially PD-1/
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in tumor growth, development, metastasis, and response PD-L1 inhibitors, also encounters resistance in some
to treatment. The development of single-cell technology patients, which may be associated with factors such as
provides a powerful tool for gaining a deeper understanding T-cell function inhibition and activation of tumor escape
of the complexity of the TME. CD244 has been shown to mechanisms. CM exhibits rich cellular heterogeneity,
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maintain the exhausted phenotype of T-cells and natural with different cell subgroups responding variably to
killer (NK) cells within the TME. A recent study found treatment. During treatment, certain cell subgroups may
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that the loss of CD244 enhances the differentiation and be more prone to evade the treatment’s effects, leading to
low
anti-tumor effects of Ly6C macrophages in melanoma the development of resistance. SOX10 serves as a marker
mouse models. Single-cell sequencing analysis of human for melanoma, with its heterogeneous expression resulting
melanoma tissue indicates that CD244 significantly in varying proliferative and invasive states. Research by
influences phagocytosis, antigen presentation, and Capparelli et al. identified a SOX10-deficient subset
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autophagy, suggesting that CD244-deficient macrophages using publicly available single-cell sequencing data.
could be an effective immunotherapy approach. Cell CRISPR knockout experiments demonstrated that the
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pyroptosis, a relatively newly discovered form of cell death, loss of SOX10 shifts the melanoma phenotype toward low
impacts TME and immunotherapy. Zhang et al. provided proliferation or high invasion states. In addition, SOX10
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insights into the cellular aspects of melanoma pathogenesis knockout cells exhibit a quiescent or dormant phenotype.
and explored pyroptosis-related genes GZMA, GSDMB, Targeted treatment with cellular inhibitors of apoptosis
NLRP1, CHMP4A, and IL18 in melanoma, revealing their protein-1/2 inhibitors improves the sustained efficacy of
deficiency linked to melanoma development. Single-cell BRAF inhibitors combined with MEK inhibitors. Given
analysis showed dysregulation of these genes in immune the significant role of SOX10 in melanoma, Purwin et al.
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cells, with GZMA and GSDMB secreted by CD8 T and integrated multi-omics data to identify a SOX10 signature
NK cells, suggesting their roles in immunotherapy. Low gene set in CM, revealing that SOX10-deficient cells are
expression of these genes correlated with higher mortality, closely associated with resistance to immune checkpoint
highlighting their prognostic value. A cell-state landscape inhibitors. Both studies revealed a cross-resistance
map of bulk tumor samples further revealed tumor relationship between the SOX10-deficient cell subgroup
heterogeneity, aiding in understanding melanoma biology and both targeted and immune checkpoint inhibitors,
and treatment. Shi et al. deconvoluted 463 skin CM bulk emphasizing the importance of addressing this subgroup
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samples based on a melanoma microenvironment cell map, in treatment strategies. Randic et al. performed scRNA-
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further identifying three distinct TME immune phenotypes: seq on NRAS-mutant melanoma samples treated with
“immune hot/active,” “immune cold-suppressed,” and MEK1/2 and CDK4/6 inhibitors, examining the transition
“immune cold-exhausted.” Correlation analysis with from drug-sensitive to drug-resistant phenotypes. The
clinical information suggests potential prognostic study identified P2RX7, involved in ion transport, as key

Volume 9 Issue 1 (2025) 8 doi: 10.36922/ejmo.5809