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Holger Heyn, head of CNAG-CRG’s Single Cell Genomics Team (Photo: CNAG-CRG).

Vall d’Hebron and CNAG develop a non-invasive method of predicting the response to immunotherapy in brain metastasis

A study led by Vall d´Hebron Institute of Oncology (VHIO) reveals that immune cells accessing cerebrospinal fluid faithfully recapitulate the characteristics of cells identified in brain metastases, and could therefore constitute novel biomarkers of response to immune-based therapies. The contribution of the Centro Nacional de Análisis Genómico (CNAG-CRG), based in the Barcelona Science Park, has been essential for carrying out the personalized transcriptome sequencing of all the cells analyzed by scRNA-seq technology.

The study, reported in Nature Communications, has led by Joan Seoane, director of Preclinical and Translational Research co-program at VHIO and ICREA Professor. It is the first time the characterization of immune system cells from the cerebrospinal fluid have been studied as a non-invasive method of predicting the response to immunotherapy of patients with cerebral metastases.

Brain metastases are the most frequent tumor of the brain, with a dismal prognosis. While a fraction of patients benefit from treatment with immune checkpoint inhibitors, the majority do not. To predict response to these therapies necessitates the characterization of tumor specimens. Due to the anatomical location of brain tumors and the risk of surgical procedures, accessing samples from brain malignancies is challenging.

Immune checkpoint inhibitors including anti-PD1, anti-PD-L1, and anti-CTLA4, have shown significant clinical benefits in patients with progressive or metastatic solid tumors, including some brain metastasis. Notably, these immune-based therapies have improved outcomes for some of those suffering from lung cancer and melanoma. Together, these tumor types (represent between 30-40% of all cancers), along with breast cancer, are three common malignancies that lead to brain metastases.

“One of the major challenges in improving outcomes for patients suffering from brain metastases caused by these cancers is that new lesions can differ immensely from the primary tumor, and thus respond in a different way to immune-based therapies,” observes Joan Seoane, co-Corresponding Author of the study.

To test this hypothesis, Joan Seoane’s team analyzed samples from 48 patients with brain metastasis. These samples were obtained thanks to the generosity of patients receiving treatment at our Vall d’Hebron University Hospital (HUVH), as well as the Hospital Clínic in Barcelona.

The study was also carried out in collaboration with researchers at the Centro Nacional de Análisis Genómico (CNAG-CRG), Barcelona. Directed by Holger Heyn head of CNAG-CRG’s Single Cell Genomics Team, they performed single cell transcriptome sequencing of around 6000 cells by scRNA-seq technology.

“Single cell transcriptome sequencing provides the highest resolution for the detection and monitoring of several different diseases. The identification of clonal T-cells in both metastasis and liquid biopsy is of particular interest. We have shown that the sequencing of T-cell receptors provides a cellular barcode that can be assessed outside of the tumor. Importantly, this approach opens up new avenues for the detection of systemic disease”, concludes Holger Heyn, co-Corresponding Author of the study.

» Reference article: Rubio-Perez, C., Planas-Rigol, E., Trincado, J.L. et al. Immune cell profiling of the cerebrospinal fluid enables the characterization of the brain metastasis microenvironment. Nat Commun 12, 1503 (2021).

» More information:  CNAG [+] and VHIO [+] websites