Spatial tumor immune microenvironment phenotypes in ovarian cancer
(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.
(Less)
- author
- Mateiou, Claudia ; Lokhande, Lavanya LU ; Diep, Lan Hoa LU ; Knulst, Mattis LU ; Carlsson, Elias LU ; Ek, Sara LU ; Sundfeldt, Karin and Gerdtsson, Anna LU
- organization
- publishing date
- 2024-12
- 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}}, }