Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer.
We investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT).84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose o...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4559430?pdf=render |
id |
doaj-2d05ac481d524658bb15266c86ee9a39 |
---|---|
record_format |
Article |
spelling |
doaj-2d05ac481d524658bb15266c86ee9a392020-11-24T21:26:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013665410.1371/journal.pone.0136654Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer.Marco PetrilloGian Franco ZannoniEnrica MartinelliLuigi Pedone AnchoraGabriella FerrandinaGiovanna TropeanoAnna FagottiGiovanni ScambiaWe investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT).84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2) was finally calculated.At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001). Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor) to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029). At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037) emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019), and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037) survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis.Polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC.http://europepmc.org/articles/PMC4559430?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marco Petrillo Gian Franco Zannoni Enrica Martinelli Luigi Pedone Anchora Gabriella Ferrandina Giovanna Tropeano Anna Fagotti Giovanni Scambia |
spellingShingle |
Marco Petrillo Gian Franco Zannoni Enrica Martinelli Luigi Pedone Anchora Gabriella Ferrandina Giovanna Tropeano Anna Fagotti Giovanni Scambia Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer. PLoS ONE |
author_facet |
Marco Petrillo Gian Franco Zannoni Enrica Martinelli Luigi Pedone Anchora Gabriella Ferrandina Giovanna Tropeano Anna Fagotti Giovanni Scambia |
author_sort |
Marco Petrillo |
title |
Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer. |
title_short |
Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer. |
title_full |
Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer. |
title_fullStr |
Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer. |
title_full_unstemmed |
Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer. |
title_sort |
polarisation of tumor-associated macrophages toward m2 phenotype correlates with poor response to chemoradiation and reduced survival in patients with locally advanced cervical cancer. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
We investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT).84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2) was finally calculated.At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001). Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor) to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029). At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037) emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019), and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037) survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis.Polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC. |
url |
http://europepmc.org/articles/PMC4559430?pdf=render |
work_keys_str_mv |
AT marcopetrillo polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer AT gianfrancozannoni polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer AT enricamartinelli polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer AT luigipedoneanchora polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer AT gabriellaferrandina polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer AT giovannatropeano polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer AT annafagotti polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer AT giovanniscambia polarisationoftumorassociatedmacrophagestowardm2phenotypecorrelateswithpoorresponsetochemoradiationandreducedsurvivalinpatientswithlocallyadvancedcervicalcancer |
_version_ |
1725979048428961792 |