Repository logo
 

Multiparameter single-cell proteomic technologies give new insights into the biology of ovarian tumors.

Published version
Peer-reviewed

Change log

Authors

Funingana, Ionut-Gabriel  ORCID logo  https://orcid.org/0000-0002-1197-2652
Huang, Ying-Wen 
Delgado Gonzalez, Antonio  ORCID logo  https://orcid.org/0000-0002-4760-8174
Donoso, Kenyi 

Abstract

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. Its diagnosis at advanced stage compounded with its excessive genomic and cellular heterogeneity make curative treatment challenging. Two critical therapeutic challenges to overcome are carboplatin resistance and lack of response to immunotherapy. Carboplatin resistance results from diverse cell autonomous mechanisms which operate in different combinations within and across tumors. The lack of response to immunotherapy is highly likely to be related to an immunosuppressive HGSOC tumor microenvironment which overrides any clinical benefit. Results from a number of studies, mainly using transcriptomics, indicate that the immune tumor microenvironment (iTME) plays a role in carboplatin response. However, in patients receiving treatment, the exact mechanistic details are unclear. During the past decade, multiplex single-cell proteomic technologies have come to the forefront of biomedical research. Mass cytometry or cytometry by time-of-flight, measures up to 60 parameters in single cells that are in suspension. Multiplex cellular imaging technologies allow simultaneous measurement of up to 60 proteins in single cells with spatial resolution and interrogation of cell-cell interactions. This review suggests that functional interplay between cell autonomous responses to carboplatin and the HGSOC immune tumor microenvironment could be clarified through the application of multiplex single-cell proteomic technologies. We conclude that for better clinical care, multiplex single-cell proteomic technologies could be an integral component of multimodal biomarker development that also includes genomics and radiomics. Collection of matched samples from patients before and on treatment will be critical to the success of these efforts.

Description

Acknowledgements: A.D-G. thanks the Fundacion Alfonso Martin Escudero for his postdoctoral fellowship. We thank Dr. Brooke Howitt for providing ovarian tissue. Figures 1, 3, and 4 were created using BioRender.


Funder: BRCA Foundation


Funder: V Foundation for Cancer Research; doi: http://dx.doi.org/10.13039/100001368


Funder: Stanford Cancer Institute, Innovation Award 2019


Funder: Stanford Cancer Institute, Innovation Award 2021


Funder: CRUK CC (crukcambridgecentre.org.uk)


Funder: Fundacion Alfonso Martin Escudero

Keywords

Carboplatin resistance, Immune tumor microenvironment, Mass cytometry/CyTOF, Multimodal biomarkers, Multiplex cellular imaging, Ovarian cancer, Single cell, Female, Humans, Carboplatin, Proteomics, Ovarian Neoplasms, Tumor Microenvironment

Journal Title

Semin Immunopathol

Conference Name

Journal ISSN

1863-2297
1863-2300

Volume Title

45

Publisher

Springer Science and Business Media LLC
Sponsorship
Ovarian Cancer Academy (W81XWH-12-1-0591)
National Cancer Institute (1R01CA234553, R21CA231280)
National Heart, Lung, and Blood Institute (P01HL10879709)
National Institute of Allergy and Infectious Diseases (U19AI057229)
Parker Institute for Cancer Immunotherapy (Bench to Bedside)