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Insights into the heterogeneity of the tumor microenvironment in lung adenocarcinoma and squamous carcinoma through single-cell transcriptomic analysis: Implications for distinct immunotherapy outcomes.
Fang, Xinyun; Li, Dianke; Wan, Shiyue; Hu, Junjie; Zhang, Peng; Jie, Dai; Chen, Linsong; Jiang, Gening; Song, Nan.
Afiliación
  • Fang X; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Li D; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Wan S; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Hu J; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Zhang P; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Jie D; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Chen L; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Jiang G; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
  • Song N; Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
J Gene Med ; 26(6): e3694, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38847309
ABSTRACT

BACKGROUND:

Immune checkpoint blockade has emerged as a key strategy to the therapy landscape of non-small cell lung cancer (NSCLC). However, notable differences in immunotherapeutic outcomes exist between the two primary NSCLC subtypes lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). This disparity may stem from the tumor immune microenvironment's heterogeneity at the transcriptome level.

METHODS:

By integrative analysis of transcriptomic characterization of 38 NSCLC patients by single-cell RNA sequencing, the present study revealed a distinct tumor microenvironment (TME) between LUAD and LUSC, with relevant results further confirmed in bulk transcriptomic and multiplex immunofluorescence (mIF) validation cohort of neoadjuvant immunotherapy patients.

RESULTS:

LUAD exhibited a more active immune microenvironment compared to LUSC. This included highly expression of HLA I/II in cancer cells, reinforced antigen presentation potential of dendritic cells and enhanced cytotoxic activity observed in T/NK cells. In LUSC, cancer cells highly expressed genes belonging to the aldo-keto reductases, glutathione S-transferases and aldehyde dehydrogenase family, negatively correlating with immunotherapy outcomes in the validation cohort of our center. Further analysis revealed elevated infiltrated cancer-associated fibroblasts (CAFs) in LUSC, which was corroborated in The Cancer Genome Atlas cohort. Corresponding increased infiltration of ADH1B+ CAFs in major pathologic response (MPR) patients and the higher presence of FAP+ CAFs in non-MPR patients were demonstrated by multiplex mIF. Moreover, upregulating immunosuppressive extracellular matrix remodeling was identified in LUSC.

CONCLUSIONS:

These comprehensive analyses advance the understanding of the differences in TME between LUAD and LUSC, offering insights for patient selection and developing subtype-specific treatment strategies.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Regulación Neoplásica de la Expresión Génica / Análisis de la Célula Individual / Microambiente Tumoral / Transcriptoma / Adenocarcinoma del Pulmón / Inmunoterapia / Neoplasias Pulmonares Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Gene Med Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Carcinoma de Células Escamosas / Regulación Neoplásica de la Expresión Génica / Análisis de la Célula Individual / Microambiente Tumoral / Transcriptoma / Adenocarcinoma del Pulmón / Inmunoterapia / Neoplasias Pulmonares Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Gene Med Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: China