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Review
. 2024 Aug 20:15:1425212.
doi: 10.3389/fimmu.2024.1425212. eCollection 2024.

Single-cell RNA sequencing in endometrial cancer: exploring the epithelial cells and the microenvironment landscape

Silvia González-Martínez  1   2   3 , Belén Pérez-Mies  2   3   4   5 , Javier Cortés  1   3   6   7   8   9   10 , José Palacios  2   3   4   5
Affiliations
Review

Single-cell RNA sequencing in endometrial cancer: exploring the epithelial cells and the microenvironment landscape

Silvia González-Martínez et al. Front Immunol. .

Abstract

Single-cell RNA sequencing (scRNA-seq) technology has emerged as a powerful tool for dissecting cellular heterogeneity and understanding the intricate biology of diseases, including cancer. Endometrial cancer (EC) stands out as the most prevalent gynecological malignancy in Europe and the second most diagnosed worldwide, yet its cellular complexity remains poorly understood. In this review, we explore the contributions of scRNA-seq studies to shed light on the tumor cells and cellular landscape of EC. We discuss the diverse tumoral and microenvironmental populations identified through scRNA-seq, highlighting the implications for understanding disease progression. Furthermore, we address potential limitations inherent in scRNA-seq studies, such as technical biases and sample size constraints, emphasizing the need for larger-scale research encompassing a broader spectrum of EC histological subtypes. Notably, a significant proportion of scRNA-seq analyses have focused on primary endometrioid carcinoma tumors, underscoring the need to incorporate additional histological and aggressive types to comprehensively capture the heterogeneity of EC. By critically evaluating the current state of scRNA-seq research in EC, this review underscores the importance of advancing towards more comprehensive studies to accelerate our understanding of this complex disease.

Keywords: cellular heterogeneity; endometrial cancer; immune landscape; single-cell RNA sequencing; tumor microenvironment.

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Conflict of interest statement

JC reports the following: Consulting/Advisor: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp&Dohme, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Scorpion Therapeutics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, Abbvie, BridgeBio, Biontech. Honoraria: Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp&Dohme, Daiichi Sankyo, Astrazeneca, Gilead, Steamline Therapeutics. Research funding to the Institution: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics,Iqvia, Queen Mary University of London. Stock: MAJ3 Capital, Leuko relative. Travel, accommodation, expenses: Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, Astrazeneca, Gilead, Merck Sharp&Dhome, Steamline Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Endometrial carcinoma histological subtypes. (A) Endometrioid endometrial carcinoma H&E 20x. (B) Serous endometrial carcinoma H&E 20x. (C) Clear cell endometrial carcinoma H&E 20x. (D) Sarcomatous component of endometrial carcinosarcoma H&E 20x. (E) Undifferentiated endometrial carcinoma H&E 40x.
Figure 2
Figure 2
Heatmaps illustrating the most representative molecular alterations in various histological and molecular subtypes of endometrial cancer. (A) Heatmap depicting the mutation frequencies of the genes most mutated across different histological and molecular subtypes of endometrial cancer. (B) Heatmap illustrating the amplification frequencies of the genes most frequently amplified in the same subtypes.
Figure 3
Figure 3
Examples of different microenvironment across endometrial tumors. (A, B) Endometrial clear cell carcinoma with dense stromal immune infiltration, predominately formed by CD8+ lymphocytes. H&E and CD8 20x. (C, D) Endometrial endometrioid carcinoma with high number of intraepithelial CD8+ lymphocytes. H&E and CD8 20x. (E, F) Endometrial serous carcinoma without immune response. Note the absence of CD8 lymphocytes. H&E and CD8 20x.
Figure 4
Figure 4
Workflow of the single-cell RNA sequencing process. Created with BioRender.com.
Figure 5
Figure 5
Distribution of cell population proportions in 8 studies of scRNA-seq in endometrial cancer. (*) The cases correspond to the 5 endometrioid endometrial cancer cases from the study by Regner et al. (29).
Figure 6
Figure 6
Representation of the cell populations in the endometrial cancer tumor microenvironment. Created with BioRender.com.
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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This review was funded by grants from the Instituto de Salud Carlos III (PMP22/00054, PI22/01892, PMP21/00107). “A way to achieve Europe” (FEDER) and by the Spanish Association Against Cancer Scientific Foundation (AECC) (Grupos Coordinados Traslacionales AECC 2018).

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