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T cells, B cells, and PD-L1 expression in esophageal and gastric adenocarcinoma before and after neoadjuvant chemotherapy : relationship with histopathological response and survival

Svensson, Maria Christina LU ; Lindén, Albin ; Nygaard, Jakob ; Borg, David LU ; Hedner, Charlotta LU ; Nodin, Björn LU ; Leandersson, Karin LU orcid and Jirström, Karin LU orcid (2021) In OncoImmunology 10(1).
Abstract

Perioperative chemotherapy enhances the survival rates for patients with esophageal and gastric (EG) adenocarcinoma, but not all patients benefit from this additional treatment. Chemotherapeutic agents have been demonstrated to alter the immune cell (IC) composition in the tumor microenvironment. Hence, there is a rationale to investigate the influence of neoadjuvant chemotherapy (NAC) on different IC subsets, to better understand and compare their utility as complementary prognostic or predictive biomarkers in a clinically relevant context. The density of T cells (CD8+ and FoxP3+), B cells (CD20+) and the expression of PD-L1 on ICs and tumor cells (TC) was assessed by immunohistochemistry on paired biopsies from primary tumors (PT)... (More)

Perioperative chemotherapy enhances the survival rates for patients with esophageal and gastric (EG) adenocarcinoma, but not all patients benefit from this additional treatment. Chemotherapeutic agents have been demonstrated to alter the immune cell (IC) composition in the tumor microenvironment. Hence, there is a rationale to investigate the influence of neoadjuvant chemotherapy (NAC) on different IC subsets, to better understand and compare their utility as complementary prognostic or predictive biomarkers in a clinically relevant context. The density of T cells (CD8+ and FoxP3+), B cells (CD20+) and the expression of PD-L1 on ICs and tumor cells (TC) was assessed by immunohistochemistry on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. The cohort encompasses 148 patients with resectable EG adenocarcinoma, all of whom received NAC. The density of CD8+ cells was decreased and the density of FoxP3+ cells and CD20+ cells was increased in PT post-NAC. PD-L1 expression was not altered following NAC. In pre-NAC specimens, high FoxP3+ density and high PD-L1 expression on ICs were favorable prognostic factors, whereas high CD8+ density was an unfavorable prognostic factor. In post-NAC specimens, however, high FoxP3+ density was an unfavorable prognostic factor, and high PD-L1 expression on TC was associated with a shorter survival. There were no significant associations between IC density or PD-L1 expression in PT pre-NAC and histopathological regression. These findings propose that NAC might alter the density and prognostic impact of some IC subsets in EG adenocarcinoma.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Esophageal cancer, gastric cancer, neoadjuvant chemotherapy, T-cells, B-cells, PD-L1 expression
in
OncoImmunology
volume
10
issue
1
article number
1921443
pages
14 pages
publisher
Landes Bioscience
external identifiers
  • scopus:85106323859
  • pmid:34104541
ISSN
2162-4011
DOI
10.1080/2162402X.2021.1921443
language
English
LU publication?
yes
id
946bdf31-f18f-4a08-8e7c-5390cf81c7e1
date added to LUP
2021-06-10 10:02:29
date last changed
2024-07-13 14:46:15
@article{946bdf31-f18f-4a08-8e7c-5390cf81c7e1,
  abstract     = {{<p>Perioperative chemotherapy enhances the survival rates for patients with esophageal and gastric (EG) adenocarcinoma, but not all patients benefit from this additional treatment. Chemotherapeutic agents have been demonstrated to alter the immune cell (IC) composition in the tumor microenvironment. Hence, there is a rationale to investigate the influence of neoadjuvant chemotherapy (NAC) on different IC subsets, to better understand and compare their utility as complementary prognostic or predictive biomarkers in a clinically relevant context. The density of T cells (CD8+ and FoxP3+), B cells (CD20+) and the expression of PD-L1 on ICs and tumor cells (TC) was assessed by immunohistochemistry on paired biopsies from primary tumors (PT) pre-NAC, and resected PT and lymph node metastases post-NAC. The cohort encompasses 148 patients with resectable EG adenocarcinoma, all of whom received NAC. The density of CD8+ cells was decreased and the density of FoxP3+ cells and CD20+ cells was increased in PT post-NAC. PD-L1 expression was not altered following NAC. In pre-NAC specimens, high FoxP3+ density and high PD-L1 expression on ICs were favorable prognostic factors, whereas high CD8+ density was an unfavorable prognostic factor. In post-NAC specimens, however, high FoxP3+ density was an unfavorable prognostic factor, and high PD-L1 expression on TC was associated with a shorter survival. There were no significant associations between IC density or PD-L1 expression in PT pre-NAC and histopathological regression. These findings propose that NAC might alter the density and prognostic impact of some IC subsets in EG adenocarcinoma.</p>}},
  author       = {{Svensson, Maria Christina and Lindén, Albin and Nygaard, Jakob and Borg, David and Hedner, Charlotta and Nodin, Björn and Leandersson, Karin and Jirström, Karin}},
  issn         = {{2162-4011}},
  keywords     = {{Esophageal cancer; gastric cancer; neoadjuvant chemotherapy; T-cells; B-cells; PD-L1 expression}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{1}},
  publisher    = {{Landes Bioscience}},
  series       = {{OncoImmunology}},
  title        = {{T cells, B cells, and PD-L1 expression in esophageal and gastric adenocarcinoma before and after neoadjuvant chemotherapy : relationship with histopathological response and survival}},
  url          = {{http://dx.doi.org/10.1080/2162402X.2021.1921443}},
  doi          = {{10.1080/2162402X.2021.1921443}},
  volume       = {{10}},
  year         = {{2021}},
}