Poor Clinical Outcome in Metastatic Melanoma is Associated with a MicroRNA-modulated Immunosuppressive Tumor Microenvironment

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2020 Feb 7

PMID 32024530

Citations 19

Authors

Natasha A N Jorge

Jessica G V Cruz

Marco Antonio M Pretti

Martin H Bonamino

Patricia A Possik

Mariana Boroni

Affiliations

Soon will be listed here.

Abstract

Background: Interaction between malignant cells and immune cells that reside within the tumor microenvironment (TME) modulate different aspects of tumor development and progression. Recent works showed the importance of miRNA-containing extracellular vesicles in this crosstalk.

Methods: Interested in understanding the interplay between melanoma and immune-related TME cells, we characterized the TCGA's metastatic melanoma samples according to their tumor microenvironment profiles, HLA-I neoepitopes, transcriptome profile and classified them into three groups. Moreover, we combined our results with melanoma single-cell gene expression and public miRNA data to better characterize the regulatory network of circulating miRNAs and their targets related to immune evasion and microenvironment response.

Results: The group associated with a worse prognosis showed phenotypic characteristics that favor immune evasion, including a strong signature of suppressor cells and less stable neoantigen:HLA-I complexes. Conversely, the group with better prognosis was marked by enrichment in lymphocyte and MHC signatures. By analyzing publicly available melanoma single-cell RNA and microvesicle microRNAs sequencing data we identified circulating microRNAs potentially involved in the crosstalk between tumor and TME cells. Candidate miRNA/target gene pairs with previously reported roles in tumor progression and immune escape mechanisms were further investigated and demonstrated to impact patient's overall survival not only in melanoma but across different tumor types.

Conclusion: Our results underscore the impact of tumor-microenvironment interactions on disease outcomes and reveal potential non-invasive biomarkers of prognosis and treatment response.

Citing Articles

The role of cancer-associated fibroblasts and exosomal miRNAs-mediated intercellular communication in the tumor microenvironment and the biology of carcinogenesis: a systematic review.

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CATD: a reproducible pipeline for selecting cell-type deconvolution methods across tissues.

Pournara A, Miao Z, Beker O, Nolte N, Brazma A, Papatheodorou I Bioinform Adv. 2024; 4(1):vbae048.

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The extracellular vesicles targeting tumor microenvironment: a promising therapeutic strategy for melanoma.

Li Y, Liu F Front Immunol. 2023; 14:1200249.

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The role of tumor-infiltrating lymphocytes in triple-negative breast cancer and the research progress of adoptive cell therapy.

Li R, Cao L Front Immunol. 2023; 14:1194020.

PMID: 37275874 PMC: 10233026. DOI: 10.3389/fimmu.2023.1194020.

Metastatic Melanoma: Liquid Biopsy as a New Precision Medicine Approach.

Ricciardi E, Giordani E, Ziccheddu G, Falcone I, Giacomini P, Fanciulli M Int J Mol Sci. 2023; 24(4).

PMID: 36835424 PMC: 9962821. DOI: 10.3390/ijms24044014.

References

Topalian S, Drake C, Pardoll D . Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015; 27(4):450-61. PMC: 4400238. DOI: 10.1016/j.ccell.2015.03.001. View

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

Quail D, Joyce J . Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013; 19(11):1423-37. PMC: 3954707. DOI: 10.1038/nm.3394. View

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y . Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12(5):453-7. PMC: 4739640. DOI: 10.1038/nmeth.3337. View

Reuben A, Spencer C, Prieto P, Gopalakrishnan V, Reddy S, Miller J . Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. NPJ Genom Med. 2017; 2. PMC: 5557036. DOI: 10.1038/s41525-017-0013-8. View

Bolotin D, Poslavsky S, Mitrophanov I, Shugay M, Mamedov I, Putintseva E . MiXCR: software for comprehensive adaptive immunity profiling. Nat Methods. 2015; 12(5):380-1. DOI: 10.1038/nmeth.3364. View

Goodridge J, Lee N, Burian A, Pyo C, Tykodi S, Warren E . HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway. J Immunol. 2013; 191(4):1567-77. PMC: 3732835. DOI: 10.4049/jimmunol.1300080. View

Alexandrov L, Nik-Zainal S, Wedge D, Aparicio S, Behjati S, Biankin A . Signatures of mutational processes in human cancer. Nature. 2013; 500(7463):415-21. PMC: 3776390. DOI: 10.1038/nature12477. View

Tirosh I, Izar B, Prakadan S, Wadsworth 2nd M, Treacy D, Trombetta J . Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016; 352(6282):189-96. PMC: 4944528. DOI: 10.1126/science.aad0501. View

10.

Ghandi M, Huang F, Jane-Valbuena J, Kryukov G, Lo C, McDonald 3rd E . Next-generation characterization of the Cancer Cell Line Encyclopedia. Nature. 2019; 569(7757):503-508. PMC: 6697103. DOI: 10.1038/s41586-019-1186-3. View

11.

Mao X, Wang C, Liu D, Zhang X, Wang L, Yan M . Hypoxia upregulates HIG2 expression and contributes to bevacizumab resistance in glioblastoma. Oncotarget. 2016; 7(30):47808-47820. PMC: 5216980. DOI: 10.18632/oncotarget.10029. View

12.

Kogure A, Kosaka N, Ochiya T . Cross-talk between cancer cells and their neighbors via miRNA in extracellular vesicles: an emerging player in cancer metastasis. J Biomed Sci. 2019; 26(1):7. PMC: 6330499. DOI: 10.1186/s12929-019-0500-6. View

13.

Dulberger C, McMurtrey C, Holzemer A, Neu K, Liu V, Steinbach A . Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through Interactions with NK Cell Receptors. Immunity. 2017; 46(6):1018-1029.e7. PMC: 5523829. DOI: 10.1016/j.immuni.2017.06.002. View

14.

Dudley M, Wunderlich J, Robbins P, Yang J, Hwu P, Schwartzentruber D . Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002; 298(5594):850-4. PMC: 1764179. DOI: 10.1126/science.1076514. View

15.

Zhou B, Wang S, Mayr C, Bartel D, Lodish H . miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci U S A. 2007; 104(17):7080-5. PMC: 1855395. DOI: 10.1073/pnas.0702409104. View

16.

Sun X, Zhang C, Cao Y, Liu E . miR-150 Suppresses Tumor Growth in Melanoma Through Downregulation of MYB. Oncol Res. 2018; 27(3):317-323. PMC: 7848275. DOI: 10.3727/096504018X15228863026239. View

17.

McAllister S, Weinberg R . The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014; 16(8):717-27. PMC: 6220424. DOI: 10.1038/ncb3015. View

18.

Segura M, Belitskaya-Levy I, Rose A, Zakrzewski J, Gaziel A, Hanniford D . Melanoma MicroRNA signature predicts post-recurrence survival. Clin Cancer Res. 2010; 16(5):1577-86. PMC: 4662869. DOI: 10.1158/1078-0432.CCR-09-2721. View

19.

Dunn G, Bruce A, Ikeda H, Old L, Schreiber R . Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11):991-8. DOI: 10.1038/ni1102-991. View

20.

Marzagalli M, Ebelt N, Manuel E . Unraveling the crosstalk between melanoma and immune cells in the tumor microenvironment. Semin Cancer Biol. 2019; 59:236-250. DOI: 10.1016/j.semcancer.2019.08.002. View