Page 16 - EJMO-9-2

Eurasian Journal of
Medicine and Oncology Single-cell sequencing for lung cancer

scRNA-seq has enabled a detailed analysis of these cells immune heterogeneity and diversity. The immune atlas
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and their roles within the TME. In a study, it was observed outlines an expanding range of immune cells, including
that combined therapy resulted in a notable increase in lymphocytes, monocytes, macrophages, natural killer cells,
normal lung epithelial cells, alongside the detection of and dendritic cells (DCs). For instance, stromal and immune
residual cancer cells, even in patients who had achieved cells undergo dynamic developmental and functional
a complete pathological response. The epithelial cells alterations, fostering a pro-tumor and immunosuppressive
were re-clustered into multiple populations, separating environment. This intricate crosstalk ultimately contributes
malignant cells from normal cells using the CopyKAT to tumor growth and resistance to therapy. 55
algorithm based on CNVs. Lu et al. found that S100P T cells are central to cancer immunotherapy. Joy A.
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47
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epithelial cells are enriched in advanced lung cancer and Pai revealed that in NSCLC patients, regulatory CD4
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+
correlate with poor prognosis. These cells exhibited higher T cells (Treg), follicular helper CD4 T cells (TFH), and
+
CNV scores in advanced lung cancer and were shown CD8 T cell subsets progressively exhaust as they approach
+
to regulate cell migration, apoptosis, and autophagy via the tumor. Wu et al., through scRNA-seq analysis of 42
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the nuclear factor kappa-B (NF-κB) and Wnt signaling tissue biopsies from stage III/IV NSCLC patients, mapped
pathways. These changes in biological pathways may the cell type-specific transcriptome landscape of advanced
provide new strategies for lung cancer treatment. Xu et al. NSCLCs, identifying rare immune cell types like follicular
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discovered that KRT81 tumor cells, a subpopulation of DCs and T helper 17 (Th17) cells. 57
+
epithelial cells, are associated with adverse prognosis in
lung adenocarcinoma (LUAD). These cells exhibited high Current research indicates that tumor-associated
activity in EMT and hypoxia pathways, indicating their high macrophages are related to tumor metastasis, invasion,
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metastatic potential. Li et al. identified distinct cellular angiogenesis, and immunosuppression. Guo et al.
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compositions in LUAD and lung squamous carcinoma found immune heterogeneity in macrophage (Mφ)
(LUSC), with alveolar type 2 cells driving heterogeneity in subtypes in NSCLC. The main Mφ subtypes were fatty
LUAD and basal cells playing a similar role in LUSC. acid binding protein 4 (FABP4)-Mφ in LUAD and secreted
phosphoprotein-1 (SPP1)-Mφ in LUSC. Tumor-infiltrating
3.3. Cancer-associated fibroblasts (CAFs) CD8 T cells undergo depletion; a high ratio of depleted to
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CAFs are a heterogeneous population of activated exhausted T cells is associated with a better prognosis in
fibroblasts within the TME, driving tumor metastasis, LUAD, and genetic markers of active tumor Tregs correlate
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immune evasion, and treatment resistance. scRNA-seq with a poor prognosis in LUAD. Yu et al. found that as
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has identified three major fibroblast subpopulations in NSCLC progressed, macrophage infiltration decreased,
non-SCLC: adventitial fibroblasts, alveolar fibroblasts, and macrophage function was altered. Low macrophage
and myofibroblasts. Alveolar and adventitial fibroblasts infiltration was found to be associated with low patient
were localized to specific regions in normal lung tissue survival based on survival analysis. Tissue inhibitor
and were associated with higher OS rates in LUAD. In of metalloproteinases 1 (TIMP1) has been reported to
contrast, myofibroblasts were linked to poorer survival regulate metastatic foci metabolism by activating the
and were associated with factors such as loss of epithelial PI3K/Akt pathway, and it has been demonstrated to be a
differentiation and TP53 mutations. 52,53 Myofibroblasts potential biomarker for the pathogenesis of LUAD through
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play a crucial role in tumor development and metastasis. protein fluorescence immunostaining experiments.
scRNA-seq analysis revealed a fibroblast-to-myofibroblast SPP1 is critical in driving macrophage polarization and
transition in LUAD, with a significant increase in facilitating lung cancer escape, highlighting its potential as
myofibroblast clusters within tumor tissue. These cells a therapeutic target for LUAD. 61
exhibited high expression of collagen genes (COL3A1, 4. Prospective clinical applications of
COL5A1, COL5A2, and COL6A3). In addition, these cells
exhibited high activity in TGFβ and JAK/STAT signaling single-cell sequencing in lung cancer
pathways, which are hallmark features of cancer-associated With the widespread application of single-cell sequencing
myofibroblasts. 54 technology in lung cancer research, its potential for
clinical translation has become more evident. Researchers
3.4. Immune cells are exploring its clinical integration to address medical
Immune cells play a crucial role in tumor progression and challenges and support lung cancer treatment. Single-
therapy response. scRNA-seq enables researchers to identify cell sequencing is being explored for its potential in early
various immune cell types and study the mechanisms diagnosis, drug resistance monitoring, and personalized
of immunosuppression, providing insights into cancer treatment of lung cancer.

Volume 9 Issue 2 (2025) 8 doi: 10.36922/ejmo.6883