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High infiltration of CD68+/CD163- macrophages is an adverse prognostic factor after neoadjuvant chemotherapy in esophageal and gastric adenocarcinoma

Svensson, Maria C LU ; Svensson, Maja LU ; Nodin, Björn LU ; Borg, David LU ; Hedner, Charlotta LU ; Hjalmarsson, Claes LU ; Leandersson, Karin LU orcid and Jirström, Karin LU orcid (2022) In Journal of Innate Immunity 14(6). p.615-628
Abstract
Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and... (More)
Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163−, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163− TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163−TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Esophageal cancer, Gastric cancer, Neoadjuvant chemotherapy, Tumor-associated macrophages
in
Journal of Innate Immunity
volume
14
issue
6
pages
615 - 628
publisher
Karger
external identifiers
  • pmid:35504250
  • scopus:85130447984
ISSN
1662-811X
DOI
10.1159/000524434
language
English
LU publication?
yes
id
39025521-4a2c-4828-98f3-6bbd5c512542
date added to LUP
2022-07-21 10:17:17
date last changed
2024-01-29 02:55:04
@article{39025521-4a2c-4828-98f3-6bbd5c512542,
  abstract     = {{Tumor-associated macrophages (TAMs) have emerged as key players in tumor immunology but demonstrate a continuum of functional states being either tumor suppressive or promoting. Moreover, chemotherapeutic agents have been shown to alter the tumor microenvironment. Perioperative chemotherapy is a standard treatment option for resectable esophageal and gastric (EG) adenocarcinoma. The aim of this study was to investigate the influence of neoadjuvant chemotherapy (NAC) on TAMs to improve the prognostication and treatment course for these patients. The study cohort comprised 148 patients, all of whom were diagnosed with resectable EG adenocarcinoma and treated with NAC. Immunohistochemistry was applied to assess the total infiltration and infiltration into tumor nests (TN) of CD68+/CD163−, CD68+/CD163+, and MARCO+ TAMs, on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. In pre-NAC specimens, high CD68+/CD163+ infiltration into TN was an unfavorable prognostic factor. No association was found between TAM density in PT pre-NAC and histopathological regression. The density of CD68+/CD163+ TAMs was increased in PT post-NAC, while the density of MARCO+ TAMs was decreased. CD68+/CD163− TAM density was not altered. In post-NAC specimens, higher total as well as TN infiltration of CD68+/CD163−TAMs were adverse prognostic factors. In conclusion, these results suggest that NAC may alter certain TAM subsets in EG adenocarcinoma, along with their functional properties and thus their prognostic value.}},
  author       = {{Svensson, Maria C and Svensson, Maja and Nodin, Björn and Borg, David and Hedner, Charlotta and Hjalmarsson, Claes and Leandersson, Karin and Jirström, Karin}},
  issn         = {{1662-811X}},
  keywords     = {{Esophageal cancer; Gastric cancer; Neoadjuvant chemotherapy; Tumor-associated macrophages}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{615--628}},
  publisher    = {{Karger}},
  series       = {{Journal of Innate Immunity}},
  title        = {{High infiltration of CD68+/CD163- macrophages is an adverse prognostic factor after neoadjuvant chemotherapy in esophageal and gastric adenocarcinoma}},
  url          = {{http://dx.doi.org/10.1159/000524434}},
  doi          = {{10.1159/000524434}},
  volume       = {{14}},
  year         = {{2022}},
}