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Spatial tumor immune microenvironment phenotypes in ovarian cancer

Mateiou, Claudia ; Lokhande, Lavanya LU ; Diep, Lan Hoa LU ; Knulst, Mattis LU ; Carlsson, Elias LU ; Ek, Sara LU ; Sundfeldt, Karin and Gerdtsson, Anna LU (2024) In NPJ precision oncology 8(1).
Abstract

Immunotherapy has largely failed in ovarian carcinoma (OC), likely due to that the vast tumor heterogeneity and variation in immune response have hampered clinical trial outcomes. Tumor-immune microenvironment (TIME) profiling may aid in stratification of OC tumors for guiding treatment selection. Here, we used Digital Spatial Profiling combined with image analysis to characterize regions of spatially distinct TIME phenotypes in OC to assess whether immune infiltration pattern can predict presence of immuno-oncology targets. Tumors with diffuse immune infiltration and increased tumor-immune spatial interactions had higher presence of IDO1, PD-L1, PD-1 and Tim-3, while focal immune niches had more CD163 macrophages and a preliminary... (More)

Immunotherapy has largely failed in ovarian carcinoma (OC), likely due to that the vast tumor heterogeneity and variation in immune response have hampered clinical trial outcomes. Tumor-immune microenvironment (TIME) profiling may aid in stratification of OC tumors for guiding treatment selection. Here, we used Digital Spatial Profiling combined with image analysis to characterize regions of spatially distinct TIME phenotypes in OC to assess whether immune infiltration pattern can predict presence of immuno-oncology targets. Tumors with diffuse immune infiltration and increased tumor-immune spatial interactions had higher presence of IDO1, PD-L1, PD-1 and Tim-3, while focal immune niches had more CD163 macrophages and a preliminary worse outcome. Immune exclusion was associated with presence of Tregs and Fibronectin. High-grade serous OC showed an overall stronger immune response and presence of multiple targetable checkpoints. Low-grade serous OC was associated with diffuse infiltration and a high expression of STING, while endometrioid OC had higher presence of CTLA-4. Mucinous and clear cell OC were dominated by focal immune clusters and immune-excluded regions, with mucinous tumors displaying T-cell rich immune niches.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
NPJ precision oncology
volume
8
issue
1
article number
148
publisher
Springer Nature
external identifiers
  • scopus:85199042588
  • pmid:39026018
ISSN
2397-768X
DOI
10.1038/s41698-024-00640-8
language
English
LU publication?
yes
id
c72d6d10-cc8f-4d0c-8eec-bc3b34dcbc0f
date added to LUP
2024-08-30 14:44:57
date last changed
2024-09-27 17:03:30
@article{c72d6d10-cc8f-4d0c-8eec-bc3b34dcbc0f,
  abstract     = {{<p>Immunotherapy has largely failed in ovarian carcinoma (OC), likely due to that the vast tumor heterogeneity and variation in immune response have hampered clinical trial outcomes. Tumor-immune microenvironment (TIME) profiling may aid in stratification of OC tumors for guiding treatment selection. Here, we used Digital Spatial Profiling combined with image analysis to characterize regions of spatially distinct TIME phenotypes in OC to assess whether immune infiltration pattern can predict presence of immuno-oncology targets. Tumors with diffuse immune infiltration and increased tumor-immune spatial interactions had higher presence of IDO1, PD-L1, PD-1 and Tim-3, while focal immune niches had more CD163 macrophages and a preliminary worse outcome. Immune exclusion was associated with presence of Tregs and Fibronectin. High-grade serous OC showed an overall stronger immune response and presence of multiple targetable checkpoints. Low-grade serous OC was associated with diffuse infiltration and a high expression of STING, while endometrioid OC had higher presence of CTLA-4. Mucinous and clear cell OC were dominated by focal immune clusters and immune-excluded regions, with mucinous tumors displaying T-cell rich immune niches.</p>}},
  author       = {{Mateiou, Claudia and Lokhande, Lavanya and Diep, Lan Hoa and Knulst, Mattis and Carlsson, Elias and Ek, Sara and Sundfeldt, Karin and Gerdtsson, Anna}},
  issn         = {{2397-768X}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Springer Nature}},
  series       = {{NPJ precision oncology}},
  title        = {{Spatial tumor immune microenvironment phenotypes in ovarian cancer}},
  url          = {{http://dx.doi.org/10.1038/s41698-024-00640-8}},
  doi          = {{10.1038/s41698-024-00640-8}},
  volume       = {{8}},
  year         = {{2024}},
}