VHIO has a new platform to unravel the complexity of tumor cells.

Compilation
Behind the acronym “Unique” lies a new next-generation single-cell cross-sectional sequencing platform. Subsidized by the “la Caixa” Foundation, it will be integrated into the core technology platforms of the Vall d’Hebron Institute of Oncology (VHIO), which is part of the Val d’Hebron campus.

Your full name, “Understanding cancer through single cell sequencing: CaixaResearch Platform’, reveals the purpose for which it was designed. This makes it possible to uncover genetic expression programs in tumor tissue and peripheral blood samples and thus characterize expression patterns cell by cell. That is, to know which genes are expressed or cease to be expressed in a certain way. “We have gone from a vague global view of the behavior of thousands of cells to thousands of complete views of each cell,” emphasizes Dr. Marcos Malumbres, ICREA Professor, Director of the Systems Oncology Program and Leader of the VHIO Cell Cycle and Cancer Group.

Implementation of the UNIQUE CaixaResearch platform with technology unicellular or one cell will allow VHIO researchers to address new scientific questions. This new paradigm will help to better understand the complexity of tumors.find new therapeutic solutions and biomarkers that will improve the care of cancer patients.

Their heterogeneity is a major obstacle that limits the effectiveness of targeted therapies and compromises treatment outcomes. “Modern approaches to mass sequencing of samples give us insight into tumor. But the truth is that a tumor contains cells with different characteristics and malignant potential, which constantly change during tumor evolution or in response to treatment.“, add Dr. Malumbres.

This new paradigm will help to better understand the complexity of tumors, find new therapeutic solutions and biomarkers that will improve the care of cancer patients.

A single tumor can contain millions of cells from a wide variety of tumor populations and types., therefore single-cell analysis is required to study this heterogeneity. In addition, it would allow the identification of different cell subpopulations and the roles they play, or the discovery of new tumor biomarkers of cancer that were considered well characterized. Added to this is that researchers will be able to better understand the response to treatment or study the evolution of tumors over time, the different stages and how they responded to different treatments.

Latest generation equipment

“Single cell sequencing allows us to detect and characterize populations of rare stem cells present in the tumor microenvironment.”added Dr. Elena Serrano, VHIO High Technology Coordinator. They are responsible for therapy resistance and tumor relapse. This also opens up the possibility of identifying latent tumor cells causing metastases; low levels of circulating tumor cells and immune cells, which may have functional and clinical significance.

To achieve these goals, the platform has three modern equipment integrated into basic transversal technological platforms of VChIO. On the one hand, it includes the team Parsotics are able to isolate circulating tumor cells using liquid biopsy. Along with this, another command Chromium (10x Genomics), which separates tumor cells between tissue cells and circulating cells one by one and prepares them for individual sequencing.

There is also a microscope on the platform Watering can DMi8 equipped with Thunder technology and CytAssist device (10x genomics). Thanks to its equipment, it is possible to determine the location of each tumor cell, knowing which genes each of them expresses.

The platform is equipped with three state-of-the-art hardware integrated into the core of VHIO’s transversal technology platforms.

Given the enormous amount of data that will be generated, processing and interpreting it will be key. For what VHIO Bioinformatics Department, led by Dr. Lara Nonell, will take on these challenges by combining this information with other available technologies, as well as integrating them with clinical data and thereby identifying biomarkers of response.

Multidisciplinary teams

Various VHIO research groups are already conducting sequencing studies. unicellular together with external collaborators. With the introduction of this new platform, they will be able to carry out their research. ‘in the house’. The medium-term goal is to introduce this technology into the clinical environment. and facilitate the translation of research into new treatments that patients can benefit from.

In that Cell Cycle and Cancer Laboratory led by Dr. Malumbres, this technology is already in use. For example, to study patterns of intercellular expression in circulating tumor cells in advanced hormone receptor-positive breast cancer. This could shed light on why some tumors become resistant to treatment.

Other areas such as Antitumor therapy modeling groupheaded by ICREA Professor Dr. Laura Soucekthey also use it for “Identify immune cell populations in the tumor microenvironment of non-small cell lung cancer and melanoma.” In doing so, they observe the effect of inhibiting a specific protein on tumor immune suppression, and then search for new formulas to reactivate the immune system against the tumor.

The platform’s technology is already used in breast, lung and brain cancer research, tumor and neoantigen identification, and spatial transcriptomics.

“Our group has conducted extensive research on brain metastases,” confirms Dr Joanne Seoane, Professor at ICREA and Head of the VHIO Gene Expression Group. “The UNIQUE platform will allow us to study which genes are expressed by cells from samples of melanoma and non-small cell lung cancer brain metastases from patients undergoing treatment, as well as the characteristics of immune cells surrounding the tumor, to try to identify biomarkers that may serve as new therapeutic targets or predict patient response to treatment.”

Dr. Alena Gros, Head of the Immunotherapy and Cancer Immunology Groupis working on various projects that use single-cell sequencing to analyze T-cell receptors (TCRs) and differentially expressed tumor-infiltrating lymphocyte (TIL) and circulating lymphocyte genes that contribute to tumor and neoantigen recognition. “Our goal is to harness the potential of this technology to detect, monitor and exploit antitumor responses in cancer patients.”.

The new platform will also make it possible to launch spatial transcriptomics projects, that is, to find out which genes are expressed in different areas of the tumor and tumor microenvironment. For example, he Prostate Cancer Translational Research Group led by Dr. Joaquín Mateowill use this technology to study biopsies before, during and after hormonal treatment for advanced prostate cancer and thus better understand how tumor heterogeneity adapts to treatment, which is relevant for the development of new treatment strategies.