Page 13 - EJMO-9-1

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

practice. Guerrero-Juarez et al. analyzed scRNA-seq data 4. Single-cell RNA-seq insights into
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from BCC and surrounding skin, revealing high epithelial cutaneous SCC (cSCC)
cell heterogeneity and transcriptional lineages within BCC
tumors, suggesting that lineage-specific genes may serve 4.1. A concise overview of cSCC
as BCC biomarkers, despite non-significant expression cSCC arises from the epidermis or appendage keratinocytes
changes in bulk RNA-seq. In situ imaging identified distinct and is a prevalent malignancy in dermatology, accounting
fibroblast subpopulations, with TMEM119 fibroblasts for approximately 20% of all skin cancers. It ranks as the
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segregated across KRT14 tumor nests. Furthermore, second most common non-melanoma skin malignancy,
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CellChat analysis indicated interactions between tumor following BCC. cSCC primarily affects sun-exposed regions,
epithelial cells and fibroblasts, suggesting that BCC tumors such as the scalp, face, and dorsum of the hand. While it
may respond to fibroblast-driven inflammatory signals is characterized by low rates of metastasis and mortality,
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through WNT5A, with heat shock proteins as potential with most cases being curable through surgical excision,
therapeutic targets. On the other hand, Haensel et al. its incidence has been steadily increasing. The incidence
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identified a subpopulation of TREM2 macrophages in of cSCC ranges from 5 to 499/100,000 individuals, with a
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the highly proliferative areas surrounding BCC epithelial lifetime risk of 14 – 20% among non-Hispanic populations
tumor cells. These macrophages were found to promote in the United States. 27,28 The multifactorial etiology of
tumor epithelial cell proliferation through the JAK- cSCC is associated with several risk factors, including
STAT3 signaling pathway. In addition, Bansaccal et al. UV exposure, age, human papillomavirus infection, and
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discovered that not all epidermal cells respond uniformly immunosuppression. In addition, studies have found
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to oncogenic stimulation from SmoM2 expression, while that cSCC is more aggressive in males. Clinically and
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SmoM2 expression in mouse ear epidermis led to tumor pathologically, cSCC is classified into several types:
clonal expansion and invasion, it did not have the same superficial, nodular, infiltrative, squamous, and mucous.
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effect as dorsal skin. Single-cell analysis revealed SmoM2- Common surgical approaches comprise skin grafting, skin
expressing basal cells in the ear contained subpopulations excision, and lymph node biopsy. For advanced cases
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with features of embryonic hair follicle progenitor cells that are not suitable for surgical intervention, alternative
(EHFP), suggesting oncogene-driven reprogramming treatment modalities may include chemotherapy,
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toward EHFP-like states. Moreover, Huang et al. identified immunotherapy, and targeted therapy.
that MDK, specifically expressed in malignant cells, serves
as an independent predictor for the depth of infiltration in 4.2. The TME characteristics and disease progression
infiltrative BCC. mechanisms in cutaneous SCC
Utilizing single-cell transcriptomic analysis enables a more
3.3. The intricate relationship between the TME and comprehensive exploration of the heterogeneity of cSCC,
treatment response in BCC
encompassing cell types, gene expression profiles, immune
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Pich-Bavastro et al. integrated spatial and single-cell cell infiltration, and cell subpopulations. This approach
transcriptomics to identify T-cell-enriched immune cell furnishes detailed insights into the potential mechanisms
populations and immune-suppressive cell populations underlying cSCC development and treatment, thereby
enriched in fibroblasts and myeloid cells. It was further facilitating personalized therapy and drug development.
discovered that cancer-associated fibroblasts (CAFs) Ji et al. identified a tumor-specific keratinocyte (TSK)
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and macrophages, which exhibit protein A-mediated subgroup in cSCC and constructed a ligand-receptor
extracellular matrix remodeling features, contribute to network between tumor and stromal cells by integrating
CD8 T-cell exhaustion and immune suppression, as well spatial transcriptomic data. This approach highlighted
as resistance to immune checkpoint blockade therapy. TSK as a hub for intercellular communication. The study
Yost et al. conducted paired single-cell RNA and T-cell indicated that immune-suppressive gene expression across
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receptor sequencing on samples from patients with BCC cell subtypes suggests mechanisms involving co-inhibitory
and SCC before and after anti-PD-1 therapy. The study signals on dendritic cells, exhausted T-cells, and regulatory
revealed a phenomenon of clonal replacement among T-cell (Treg) recruitment. Zou et al. analyzed single-
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tumor-specific T-cells after PD-1 blockade therapy, with cell transcriptomic data from 13 samples across all stages
new clones emerging while existing clones decreased in of cSCC development: normal skin, AK, SCC in situ
number. This finding suggests that PD-1 blockade therapy (SCCIS), and invasive cSCC. The study found an increase
can induce dynamic changes in T-cell populations within in basal cells in SCCIS and cSCC, with a subpopulation in
the TME, potentially originating from newly introduced cSCC expressing stem cell markers, indicating impaired
T-cell clone libraries infiltrating the tumor (Table 1). differentiation. A basal cell subpopulation with higher

Volume 9 Issue 1 (2025) 5 doi: 10.36922/ejmo.5809