English
norskTissue analyses reveal a potential immune-adjuvant function of FAP-1 positive fibroblasts in non-small cell lung cancer
Permanent link
https://hdl.handle.net/10037/12712
Date
2018-02-07Type
Journal articleTidsskriftartikkel
Peer reviewed
Abstract
Objectives:
Selective targeting of cancer-associated fibroblasts (CAFs) has been proposed to synergize with immune-checkpoint inhibitors. While the roles of CAFs in cancer development are well described, their immune-regulatory properties remain incompletely understood. This study investigates correlations between CAF and immune-markers in tumor stroma from nonsmall cell lung cancer (NSCLC) patients, and examines whether a combination of CAF and immune cell scores impact patient prognosis.
Methods:
Tumor specimens from 536 primary operable stage I-III NSCLC patients were organized in tissue microarrays. Expression of protein-markers was evaluated by immunohistochemistry.
Results:
Fibroblast and stromal markers PDGFRα, PDGFRβ, FAP-1 and vimentin showed weak correlations while αSMA, and Masson’s trichrome did not correlate with any of the investigated markers. Hierarchical clustering indicated the existence of different CAF-subsets. No relevant correlations were found between any CAF-marker and the immune-markers CD3, CD4, CD8, CD20, CD68, CD1a, CD56, FoxP3 and CD45RO. High density of fibroblast-activation protein positive mesenchymal cells (CAFFAP) was associated with better prognosis in tumors with high infiltration of CD8 and CD3 T-lymphocytes.
Conclusions:
The presented data suggest that CAFs, irrespective of identity, have low influence on the degree of tumor infiltration by inflammatory- and/or immune-cells. However, CAFFAP may exert immuno-adjuvant roles in NSCLC, and targeting CAFs should be cautiously considered.
Selective targeting of cancer-associated fibroblasts (CAFs) has been proposed to synergize with immune-checkpoint inhibitors. While the roles of CAFs in cancer development are well described, their immune-regulatory properties remain incompletely understood. This study investigates correlations between CAF and immune-markers in tumor stroma from nonsmall cell lung cancer (NSCLC) patients, and examines whether a combination of CAF and immune cell scores impact patient prognosis.
Methods:
Tumor specimens from 536 primary operable stage I-III NSCLC patients were organized in tissue microarrays. Expression of protein-markers was evaluated by immunohistochemistry.
Results:
Fibroblast and stromal markers PDGFRα, PDGFRβ, FAP-1 and vimentin showed weak correlations while αSMA, and Masson’s trichrome did not correlate with any of the investigated markers. Hierarchical clustering indicated the existence of different CAF-subsets. No relevant correlations were found between any CAF-marker and the immune-markers CD3, CD4, CD8, CD20, CD68, CD1a, CD56, FoxP3 and CD45RO. High density of fibroblast-activation protein positive mesenchymal cells (CAFFAP) was associated with better prognosis in tumors with high infiltration of CD8 and CD3 T-lymphocytes.
Conclusions:
The presented data suggest that CAFs, irrespective of identity, have low influence on the degree of tumor infiltration by inflammatory- and/or immune-cells. However, CAFFAP may exert immuno-adjuvant roles in NSCLC, and targeting CAFs should be cautiously considered.
Description
Source at: http://doi.org/10.1371/journal.pone.0192157