The knowledge about the vast heterogeneity of immune receptors and their role in the anti -tumor response has gained high importance for precision cancer medicine. Scientists therefore have an immense interest to collect information and profiling data of immune receptor repertoires – T-cell receptors (TCR) and immunoglobulins.
However, research groups often face the problem that available tumor material is insufficient to perform immune repertoire profiling along with other analyses such as Exome-Seq and RNA-Seq. Additional analyses also need additional resources, which burdens the large scale clinical trials.
The idea then was to bypass these limiting factors and to extract TCR and immunoglobulin repertoires from the bulk transcriptome sequencing data of tumor RNA. RNA-Seq is routinely performed and could be a useful alternative way to obtain the intratumoral repertoires of immune receptors.
MiLaboratory LLC recently upgraded its flagship software product, MiXCR, enabling it to efficiently extract TCR and immunoglobulin repertoires from RNA-Seq data.
Using MiXCR RNA-Seq mode to analyse bulk transcriptomic data of human melanoma, the APERIM researchers demonstrated that the extracted TCR repertoires of medium and large tumor-infiltrating T cell clones are very similar to those obtained using targeted TCR profiling performed from the same RNA samples.
In this work that involved a bundle of research groups it was also shown that high intratumoral expression of clonal IgG1 antibodies is associated with the best prognosis in human melanoma.
Finally, the work demonstrates that RNA-Seq performed for the pure sorted T cells allows to extract nearly complete TCR repertoires for these cells, which converts bulk transcriptomic profiling into a powerful universal approach for the functional analysis of T and B cell subpopulations.
All these findings, which were recently published in Nature biotechnology, should help to use RNA-Seq data as a source for antigen receptor repertoire profiling, amplifying the possibilities for adaptive immunity studies and rising the chances to find further clinically relevant biomarkers for cancer immunotherapy.