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Joan Seoane et al.
of the Cancer Institute of Vall d'Hebron University in Spain used single-cell sequencing combined with T cell receptor genotyping to show lymphocytes present in brain metastases and cerebrospinal fluid, mapping brain metastases and lymphocytes matching CSF
.
The results were published online in the March 2021 issue of Nature Communications
.
- Excerpted from the article chapter
【Ref: Rubio-Perez C, et al.
Nat Commun.
2021 Mar 8; 12(1):1503.
doi: 10.
1038/s41467-021-21789-x.
】
Research background
Brain metastases are common malignant brain tumors with a poor prognosis; Immune checkpoint inhibitor (ICI) therapy may be effective in
a small percentage of patients with brain metastases.
The degree and phenotype of lymphocyte infiltration can be used to predict response to ICI, but the specificity of brain surgery often limits access to tumor specimens and affects the determination
of immunophenotype.
Joan Seoane et al.
of the Cancer Institute of Vall d'Hebron University in Spain used single-cell sequencing combined with T cell receptor genotyping to show lymphocytes present in brain metastases and cerebrospinal fluid (CSF), mapping brain metastases and lymphocyte maps matching CSF
.
The results were published online in the March 2021 issue of Nature Communications
.
Research methods
to ICI treatment.
The 50 specimens contained 8 different primary tumor types, with lung adenocarcinoma (LUAD) being the most
.
Infiltrated lymphocytes are abundant, including TAM/microglia, T cells, NK cells (CLym) and B cells; The smaller number of cells are dendritic cells (DCs) and neutrophils
.
T cells can be divided into naïve, regulatory (Treg) and cytotoxic T cells, including CD8+ T cells co-aggregated with NK cells
.
The relative proportion of cells varies widely, indicating individual heterogeneity
of tumor-infiltrating lymphocytes.
The authors found a cluster of cells with cell cycle characteristics, indicating that T cells and TAMs proliferate actively, while lymphocyte infiltration signatures
of brain transtumors can be reproduced in the cerebrospinal fluid.
Study results
The authors performed scRNA and TCR sequencing on 6 patients with matched brain metastases and CSF samples, and analyzed a total of 16 samples with 2100 high-quality cells, of which leukocytes accounted for the vast majority, called cerebrospinal fluid infiltrating leukocytes (CILs).
In CSF follow-up samples from 2 patients, an increase in CLym and naïve T cells and a large decrease
in TAM were observed after tumor resection.
Pseudo-time trajectories infer that a continuous arrangement of T cells originates from naïve T cells and ends
in a reactive/proliferative cytotoxic state and Treg.
In addition, identical TCR clones can be detected in cerebrospinal fluid at multiple sampling time points, and selected TCR clones
can be followed longitudinally.
These results suggest that analysis of CIL monitors lymphocyte invasion features
of brain metastases.
Conclusion of the study
In summary, tumor infiltrating lymphocytes, especially CD8+ T cell infiltration, can be identified by CSF analysis, and the same T-cell receptor clonal phenotype
can be detected in both brain tumors and corresponding cerebrospinal fluid.
Analysis of cerebrospinal fluid lymphocytes provides a non-invasive alternative to predict tumor response
to ICI.
