VHIO's new UNIQUE CaixaResearch platform will allow the individual analysis of the different cells that make up a tumour for the development of new therapies

The "la Caixa" Foundation has subsidised the installation of a new transversal platform for new generation single cell sequencing: UNderstanding cancer through single cell sequencing: the UNIQUE CaixaResearch platform, which will be integrated into the core technological platforms of the Vall d'Hebron Institute of Oncology (VHIO), which is part of the Vall d'Hebron Campus. 

A single tumour can have millions of cells from very different populations and tumour types, which is why single cell analysis is necessary to study tumour heterogeneity, identify different cell subpopulations and the role they play, discover new tumour biomarkers for tumours that until now were considered well characterised, better understand the response to treatment or investigate the evolution of a tumour over time, the different stages and how they have responded to different treatments. 

Tumour heterogeneity is a major obstacle that limits the efficacy of targeted therapies and compromises treatment outcomes. "Current approaches to mass sequencing of samples give us an overview of the tumour. But the truth is that the tumour contains cells with different characteristics and malignant potential that constantly change with the evolution of the tumour or in response to treatments," explains Dr Marcos Malumbres, ICREA professor, director of the Systems Oncology Programme and head of VHIO's Cell Cycle and Cancer Group, which is working with this technology with the aim of developing and testing novel therapeutic strategies and translating them into clinical practice.

The implementation of the UNIQUE CaixaResearch platform will allow VHIO researchers to address new scientific questions to better understand the complexity of tumours, find new therapeutic solutions and biomarkers that improve the care of cancer patients.

Single-cell technology makes it possible to unravel gene expression programmes in tumour tissue and peripheral blood samples and to characterise cell-by-cell expression patterns, i.e. to know which genes are or are not expressed in each cell. "We went from having a fuzzy global view of the behaviour of thousands of cells to having thousands of complete views of each cell," says Dr Malumbres.  

State-of-the-art equipment 

"Single cell sequencing allows us to detect and characterise rare stem cell populations present in the tumour microenvironment responsible for therapy resistance and tumour relapse, latent tumour cells that cause metastasis, circulating tumour cells of low abundance and immune cells that may have functional relevance and clinical significance," explains Dr Elena Serrano, coordinator of VHIO's High Technology Unit.

To meet these objectives, the UNIQUE CaixaResearch platform has three state-of-the-art units that are integrated into VHIO's core cross-cutting technology platforms. On the one hand, it includes a Parsotix equipment capable of isolating circulating tumour cells by liquid biopsy; a Chromium X equipment (10x Genomics) that separates tumour cells between tissue cells and circulating cells, one by one, and prepares them for sequencing individually.

The platform also has a Leica DMi8 microscope equipped with Thunder technology and CytAssist (10x genomics) equipment that will allow, from solid samples of the tumour, to locate the location of each of the cells in the tumour, knowing which genes are expressed by each of them. "In short," concludes Dr. Elena Serrano, "we obtain information on which genes a specific tumour cell is expressing or not and what place that cell occupies within the tumour environment. This is known as spatial transcriptomics". 

The UNIQUE CaixaResearch platform is going to generate a huge amount of data, so a key element to exploit all this information in cancer research will be the processing and interpretation of these data by VHIO's Bioinformatics Unit, led by Dr. Lara Nonell. The integration of the data obtained from the UNIQUE CaixaResearch platform with data from other available technologies, as well as the integration with clinical data, will be key to the identification of biomarkers of response. 

Several VHIO research groups are already conducting research with single-cell sequencing together with external collaborators. With the implementation of this new platform, they will be able to carry out their research in house. The medium-term goal is to implement this technology in the clinical setting and facilitate the translation of research into new treatments that can benefit patients. 

In the Cell Cycle and Cancer laboratory led by Marcos Malumbres, this technology is already being used to study cell-to-cell expression patterns in circulating tumour cells in hormone receptor-positive advanced breast cancer to try to understand why these tumours become resistant to conventional therapies.

Also, the Modelling of Antitumour Therapies Group, led by ICREA Professor Dr. Laura Soucek, a pioneer in the field of cancer research. Laura Soucek, a pioneer in Myc protein inhibition as a potential treatment in different types of cancer, uses single cell sequencing to "identify immune cell populations in the tumour microenvironment of non-small cell lung cancer and melanoma and observe the impact of Myc protein inhibition on tumour immune suppression with the aim of finding new ways to reactivate the immune system against the tumour".  

"Our group has done extensive research on brain metastasis," says Dr Joan Seoane, ICREA professor and head of VHIO's Gene Expression Group. "The UNIQUE platform will allow us to study which genes are expressed by cells from brain metastasis samples of melanoma and non-small cell lung cancer in patients undergoing treatment, as well as the characteristics of the immune cells surrounding the tumour to try to identify biomarkers that can serve as new therapeutic targets or to predict patients' response to treatment. 

Dr Alena Gros, head of the Cancer Immunotherapy and Immunology Group, works on several projects that use single-cell sequencing to analyse T-cell receptors (TCRs) and differentially expressed genes of tumour infiltrating lymphocytes (TILs) and circulating lymphocytes that contribute to tumour and neoantigen recognition. "Our goal is to use the potential of this technology to detect, monitor and exploit the anti-tumour response in cancer patients," she said. 

The new platform will also enable the implementation of spatial transcriptomics projects, i.e. knowing which genes are expressed in different areas of the tumour and tumour microenvironment. For example, the Prostate Cancer Translational Research Group, led by Dr Joaquin Mateo, will use this technology to study biopsies before, during and after hormonal treatment for advanced stage prostate cancer, and thus better understand how tumour heterogeneity adapts to treatment, which is relevant for designing new treatment strategies. 

About VHIO 

The Vall d'Hebron Institute of Oncology (VHIO), created in 2006 and integrated in the Vall d'Hebron Campus, is a reference centre in personalised medicine in oncology. Our objective is to carry out research to improve the prevention, early diagnosis and treatment of cancer thanks to a pioneering model of translational research that consists of transforming the latest discoveries made in the laboratory into early phase clinical trials and, therefore, in the development of new, more effective treatments that improve the quality of life of cancer patients. 

The VHIO is a centre that is part of the CERCA system and is accredited as a Severo Ochoa Centre of Excellence.  

All of VHIO's activities would not be possible without the support of our trustees -Generalitat de Catalunya, Fundación Cellex, Fundación "la Caixa", Fundación FERO and Fundación BBVA- and the donations of different associations, entities and individuals who contribute with their generosity so that we can make progress in cancer research.