The co-location of CD14+APOE+ cells and MMP7+ tumour cells contributed to worse immunotherapy response in non-small cell lung cancer.

Clin Transl Med

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China.

Published: September 2024

AI Article Synopsis

  • Intra-tumour immune infiltration significantly impacts the effectiveness of immunotherapy in non-small cell lung cancer (NSCLC), with two key patterns identified: immune exclusion (linked with myeloid cells) and immune activation (linked with plasma cells).
  • The study found that immune exclusion is associated with poor patient survival due to increased epithelial–mesenchymal transition and reduced immune activity, particularly marked by the presence of CD14+APOE+ cells and MMP7+ tumour cells.
  • Additionally, patients in an immunotherapy trial showing worse responses had higher levels of CD14+APOE+ and MMP7+ cells, revealing a critical link between these cell types and immune resistance mechanisms in NSCLC.

Article Abstract

Intra-tumour immune infiltration is a crucial determinant affecting immunotherapy response in non-small cell lung cancer (NSCLC). However, its phenotype and related spatial structure have remained elusive. To overcome these restrictions, we undertook a comprehensive study comprising spatial transcriptomic (ST) data (28 712 spots from six samples). We identified two distinct intra-tumour infiltration patterns: immune exclusion (characterised by myeloid cells) and immune activation (characterised by plasma cells). The immune exclusion and immune activation signatures showed adverse and favourable roles in NSCLC patients' survival, respectively. Notably, CD14+APOE+ cells were recognised as the main cell type in immune exclusion samples, with increased epithelial‒mesenchymal transition and decreased immune activities. The co-location of CD14+APOE+ cells and MMP7+ tumour cells was observed in both ST and bulk transcriptomics data, validated by multiplex immunofluorescence performed on 20 NSCLC samples. The co-location area exhibited the upregulation of proliferation-related pathways and hypoxia activities. This co-localisation inhibited T-cell infiltration and the formation of tertiary lymphoid structures. Both CD14+APOE+ cells and MMP7+ tumour cells were associated with worse survival. In an immunotherapy cohort from the ORIENT-3 clinical trial, NSCLC patients who responded unfavourably exhibited higher infiltration of CD14+APOE+ cells and MMP7+ tumour cells. Within the co-location area, the MK, SEMA3 and Macrophage migration inhibitory factor (MIF) signalling pathway was most active in cell‒cell communication. This study identified immune exclusion and activation patterns in NSCLC and the co-location of CD14+APOE+ cells and MMP7+ tumour cells as contributors to immune resistance.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347392PMC
http://dx.doi.org/10.1002/ctm2.70009DOI Listing

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The co-location of CD14+APOE+ cells and MMP7+ tumour cells contributed to worse immunotherapy response in non-small cell lung cancer.

Clin Transl Med

September 2024

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China.

Article Synopsis
  • Intra-tumour immune infiltration significantly impacts the effectiveness of immunotherapy in non-small cell lung cancer (NSCLC), with two key patterns identified: immune exclusion (linked with myeloid cells) and immune activation (linked with plasma cells).
  • The study found that immune exclusion is associated with poor patient survival due to increased epithelial–mesenchymal transition and reduced immune activity, particularly marked by the presence of CD14+APOE+ cells and MMP7+ tumour cells.
  • Additionally, patients in an immunotherapy trial showing worse responses had higher levels of CD14+APOE+ and MMP7+ cells, revealing a critical link between these cell types and immune resistance mechanisms in NSCLC.
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