Prognostic Integrated Image-Based Immune and Molecular Profiling in Early-Stage Endometrial Cancer

Horeweg, Nanda; Bruyn, Marco de; Nout, Remi A.; Stelloo, Ellen; Kedziersza, Katarzyna; León‐Castillo, Alicia; Plat, Annechien; Mertz, Kirsten D.; Osse, Michelle; Jürgenliemk-Schulz, Ina M.; Lutgens, Ludy; Jobsen, Jan J.; Steen-Banasik, Elzbieta M. van der; Smit, Vincent T.H.B.M.; Creutzberg, Carien L.; Bosse, Tjalling; Nijman, Hans W.; Koelzer, Viktor H.; Church, David N.

doi:10.1158/2326-6066.cir-20-0149

Cited by 54 publications

(68 citation statements)

References 43 publications

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“…This study applies a digital quantification method, 20 employing deep neural networks for tissue segmentation, to determine the infiltration patterns of single CD8, single CD103 and CD8CD103 TRM in HGSOC, and to investigate the impact of the spatial distribution of immune cells in the tumor microenvironment on clinical outcomes. We demonstrate that high CD8CD103 TRM infiltration is associated with improved survival in HGSOC patients; however, this survival benefit is restricted to completely debulked PDS patients.…”

Section: Discussionmentioning

confidence: 99%

“…Infiltration of three immune cell subsets was assessed; CD8 + CD103 − (single CD8), CD8 − CD103 + (single CD103) and CD8 + CD103 + TRM cells (CD8CD103 TRM) in different locations; the epithelium and stromal compartments (Figure 1). 20 Hierarchical clustering revealed that patients were clustered together based on infiltration of the various cell subsets, independent of location (Figure 2(a)). In addition, there was apparent heterogeneity in the degree of single CD8, single CD103 and CD8CD103 TRM infiltration with a subgroup of patient samples infiltrated by single CD8 cells or single CD103 cells, but not CD8CD103 TRM cells.…”

Section: Patterns Of Infiltration Of the Cd8cd103 Immune Cell Subsetsmentioning

confidence: 99%

“…The study showed greater sensitivity of automatic machine learning compared to manual quantification. 20 In this study, we applied the same innovative image-based quantification technique as Horeweg et al to address the questions; whether CD8, CD103 or both markers need to be quantified for optimal prognostication in HGSOC; and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration. We demonstrate that the prognostic benefit of CD8CD103 TRM infiltration in HGSOC is restricted to PDS treated patients with a complete debulking.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

et al. 2021

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CD103-positive tissue resident memory-like CD8 + T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions. Infiltration of CD8CD103 immune cell subsets was independent of clinicopathological factors. Our results suggest CD8CD103 TRM quantification as a superior method for prognostication compared to single CD8 or CD103 quantification. A survival benefit of CD8CD103 TRM was observed only in patients treated with primary cytoreductive surgery. Moreover, survival benefit in this group was limited to patients with no macroscopic tumor lesions after surgery. This approach provides novel insights into prognostic stratification of HGSOC patients and may contribute to personalized treatment strategies in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Patterns Of Infiltration Of the Cd8cd103 Immune Cell Subsetsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

et al. 2021

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“…We recently demonstrated that assessment of CD8 + tumor in ltrating Tlymphocytes (TILs) improves prognostication beyond clinicopathological risk factors and molecular class. 1 In another study, we found that T-cell responses led to B-cell driven immune responses via the secretion of CLCX13, a key driver of B-cell recruitment. 2 Expression of CLCX13 was associated with the formation of B-cell aggregates in and around ECs in the presence of high endothelial venules (HEV), germinal B-cells centers and dendritic cells surrounded by a rim of T-cells.…”

Section: Introductionmentioning

confidence: 93%

“…2 Immunohistochemistry for CD8 + and CD20 + was carried out using a modi cation of a previously reported protocol. 1,2 ). Unstained epithelium and stromal broblasts served as internal negative controls.…”

Section: Patient Materialsmentioning

confidence: 99%

Tertiary lymphoid structures critical for prognosis in endometrial cancer patients - a TransPORTEC study

Horeweg

Workel

Loiero

et al. 2021

Preprint

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B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigated the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells showed presence of activated/memory B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis showed association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence showed L1CAM expression in mature TLS localized in the myometrial wall or at the tumor invasive border, independent of L1CAM expression the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank were evaluated. TLS were found in 19%, predominantly in mismatch-repair deficient and polymerase-epsilon mutant EC. Multivariable Cox regression analysis showed strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker.Statement of significance Tertiary lymphoid structures have a pivotal role in the immune response against endometrial cancer. Presence of mature tertiary lymphoid structures can be easily assessed using L1CAM immunohistochemistry and has independent favorable predictive value for recurrence and endometrial cancer-specific survival.

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Identification of a disulfidptosis‐related prognostic signature for prediction of the effect of treatment in patients with endometrial carcinoma

Peng,

Gao,

Cao

et al. 2024

Cancer Innovation

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BackgroundDisulfide, an essential compounds family, has diverse biological activity and can affect the dynamic balance between physiological and pathological states. A recently published study found that aberrant accumulation of disulfide had a lethal effect on cells. This mechanism of cell death, named disulfidptosis, differs from other known cell death mechanisms, including cuproptosis, apoptosis, necroptosis, and pyroptosis. The relationship between disulfidptosis and development of cancer, in particular endometrial carcinoma, remains unclear.MethodsTo address this knowledge gap, we performed a preliminary analysis of samples from The Cancer Genome Atlas database. The samples were divided equally into a training group and a test group. A total of 2308 differentially expressed genes were extracted, and 11 were used to construct a prognostic model.ResultsBased on the risk score calculated using the prognostic model, the samples were divided into a high‐risk group and a low‐risk group. Survival time, tumor mutation burden, and microsatellite instability scores differed significantly between the two groups. Furthermore, a between‐group difference in treatment effect was predicted. Comparison with other models in the literature indicated that this prognostic model had better predictive anility.ConclusionThe results of this study provide a general framework for understanding the relationship between disulfidptosis and endometrial cancer that could be used for clinical evaluation and selection of appropriate personalized treatment strategies.

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Prognostic Integrated Image-Based Immune and Molecular Profiling in Early-Stage Endometrial Cancer

Cited by 54 publications

References 43 publications

Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

Prognostic image-based quantification of CD8CD103 T cell subsets in high-grade serous ovarian cancer patients

Tertiary lymphoid structures critical for prognosis in endometrial cancer patients - a TransPORTEC study

Identification of a disulfidptosis‐related prognostic signature for prediction of the effect of treatment in patients with endometrial carcinoma

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