Identification of tumour‐infiltrating myeloid subsets associated with overall survival in lung squamous cell carcinoma
Open accessAbstract
Lung squamous cell carcinoma (LUSC) is a primary subtype of lung cancer with limited therapeutic options and poor prognosis, and tumour‐infiltrating myeloid cells (TIMs) are key regulators of LUSC. However, the correlation between the abundance of TIM subtypes and clinical outcomes of LUSC remains unexplored. This study aimed to develop and validate a prognostic model for low‐ and high‐risk patients with LUSC based on myeloid cell microenvironments. TIM markers in the tumoural (T) and stromal (S) regions were quantified using immunohistochemistry for 502 LUSC patients. L1‐penalized Cox regression was used to develop a myeloid survival score (MSS) model based on the training cohort, followed by validation in distinct cohorts from multiple centres. RNA sequencing and immunostaining were used to examine the mechanisms of myeloid cells in LUSC progression and predict potential drug targets and therapeutic agents. Of the 12 myeloid markers, CD163T, CD163S, and S100A12T were highly associated with overall survival (OS) in LUSC patients. The MSS of the three myeloid signatures accurately categorized LUSC patients into risk categories, with an observable difference in OS between the training and validation cohorts. Tumours with high MSS were associated with enhanced antioxidative ability and hedgehog signalling and a shift to a more pro‐tumorigenic microenvironment, accompanied by a reduced tumour cell immunogenicity and increased CD8 + T cell exhaustion patterns. Additionally, in high‐risk patients, potential drug targets and compounds regulating hedgehog signalling were identified. Our study provides the first prognostic myeloid signature for LUSC, which may help advance precision medicine. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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The copper-complex radiosensitizes ALDH1-positive carcinoma cells by inhibiting ALDH1 and downregulating the PI3K/Akt pathway, particularly enhancing the radiosensitivity of tumor-initiating cells.
“In vitro and in vivo studies showed that the copper-complex radiosensitizes ALDH1-positive carcinoma cells by inhibiting ALDH1 and downregulating the phosphoinositide 3-kinase (PI3K)/Akt pathway, particularly enhancing the radiosensitivity of tumor-initiating cells.79”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [79]
The Discussion (page unavailable) says disulfiram inhibits GLI1 in a copper-dependent manner. The References list separate studies on disulfiram/copper targeting an ALDH-positive population through ALDH1A1 inhibition and on copper-related radiosensitization. Our copy does not report that a copper-complex radiosensitizes ALDH1-positive carcinoma cells by inhibiting ALDH1 and downregulating PI3K/Akt, or that it particularly sensitizes tumor-initiating cells. (LLM, conf=0.80)
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- Authors
- Lu, J., Duan, Y., Liu, P., He, X., Yang, Y., Zhang, R., & Weng, L.
- Affiliations
- Central South University (CN)
- Department of Oncology, Xiangya Cancer Center, Xiangya Hospital Central South University Changsha PR China
- Hunan Normal University (CN)
- Corresponding author
- Weng, Liang
- Venue
- The Journal of Pathology
- Publisher
- Wiley
- Published
- 2022-11-16
- Volume
- 259
- Issue
- 1
- Pages
- 21-34
- ISSN
- 0022-3417 (ISSN-L)
- 1096-9896
- PMC
- PMC10100161
- OpenAlex
- W4298086517
- Cited by
- 6
- References
- 72
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1
- FWCI
- 0.38
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Pathology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Huxiang Youth Talent Support Program (2019RS1009)
- National Natural Science Foundation of China (81900199, 81974465)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- lung squamous cell carcinoma, prognostic signature, overall survival, CD163, S100A12, tumor microenvironment, Hedgehog signaling, antioxidant capacity, CD8+ T cell exhaustion, tumor immunogenicity, therapeutic target
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Humans, Lung, Lung Neoplasms, Prognosis, Biomarkers, Tumor, Hedgehog Proteins, Tumor Microenvironment
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