Spatial genomics uncovers cytokines promoting ovarian tumour heterogeneity and immunotherapy resistance

Gurkan Mollaoglu , Brian D. Brown , Alessia Baccarini

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (2) : e70248

PDF
Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (2) : e70248 DOI: 10.1002/ctm2.70248
INVITED LETTER

Spatial genomics uncovers cytokines promoting ovarian tumour heterogeneity and immunotherapy resistance

Author information +
History +
PDF

Keywords

immunotherapy / IL-4 / ovarian cancer / tumour immunology

Cite this article

Download citation ▾
Gurkan Mollaoglu, Brian D. Brown, Alessia Baccarini. Spatial genomics uncovers cytokines promoting ovarian tumour heterogeneity and immunotherapy resistance. Clinical and Translational Medicine, 2025, 15(2): e70248 DOI:10.1002/ctm2.70248

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Konstantinopoulos PA, Matulonis UA. Clinical and translational advances in ovarian cancer therapy. Nat Cancer. 2023; 4: 1239-1257.

[2]

Ghisoni E, Morotti M, Sarivalasis A, et al. Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach. Nat Rev Clin Oncol. 2024; 21: 801-817.

[3]

Kandalaft LE, Dangaj Laniti D, Coukos G. Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation. Nat Rev Cancer. 2022; 22: 640-656.

[4]

Veneziani AC, Gonzalez-Ochoa E, Alqaisi H, et al. Heterogeneity and treatment landscape of ovarian carcinoma. Nat Rev Clin Oncol. 2023; 20: 820-842.

[5]

Bell D, Berchuck A, Birrer M, et al. Integrated genomic analyses of ovarian carcinoma. Nature. 2011; 474: 609-615.

[6]

Zhang AW, McPherson A, Milne K, et al. Interfaces of malignant and immunologic clonal dynamics in ovarian cancer. Cell. 2018; 173: 1755-1769.e22.

[7]

Izar B, Tirosh I, Stover EH, et al. A single-cell landscape of high-grade serous ovarian cancer. Nat Med. 2020; 26: 1271-1279.

[8]

Desbois M, Udyavar AR, Ryner L, et al. Integrated digital pathology and transcriptome analysis identifies molecular mediators of T-cell exclusion in ovarian cancer. Nat Commun. 2020; 11: 5583.

[9]

Hornburg M, Desbois M, Lu S, et al. Single-cell dissection of cellular components and interactions shaping the tumor immune phenotypes in ovarian cancer. Cancer Cell. 2021; 39: 928-944.e6.

[10]

Vázquez-García I, Uhlitz F, Ceglia N, et al. Ovarian cancer mutational processes drive site-specific immune evasion. Nature. 2022; 612: 778-786. doi:10.1038/s41586-022-05496-1

[11]

Binnewies M, Roberts EW, Kersten K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018; 24: 541-550.

[12]

Mollaoglu G, Tepper A, Falcomatà C, et al. Ovarian cancer-derived IL-4 promotes immunotherapy resistance. Cell. 2024; 187: 7492-7510.e22.

[13]

Dhainaut M, Rose SA, Akturk G, et al. Spatial CRISPR genomics identifies regulators of the tumor microenvironment. Cell. 2022; 185: 1223-1239.e20.

[14]

Wroblewska A, Dhainaut M, Ben-Zvi B, et al. Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens. Cell. 2018; 175: 1141-1155.e16.

[15]

Mahmood N, Mihalcioiu C, Rabbani SA. Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front Oncol. 2018; 8: 24.

[16]

Zhai B-T, Tian H, Sun J, et al. Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer. J Transl Med. 2022; 20: 135.

[17]

LaMarche NM, Hegde S, Park MD, et al. An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis. Nature. 2024; 625: 166-174.

[18]

Stewart CM, Siegler EL, Sakemura RL, et al. IL-4 drives exhaustion of CD8+ CART cells. Nat Commun. 2024; 15: 7921.

[19]

Feng B, Bai Z, Zhou X, et al. The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer. Nature. 2024; 634: 712-720.

RIGHTS & PERMISSIONS

2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

AI Summary AI Mindmap
PDF

121

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/