New Cancer Receptor Families Discovered via Immune Repertoire Mining

Researchers Map 150,000 Tumors to Find Shared T Cell Receptors

Researchers analyzed bulk RNA sequencing data and clinical records from more than 150,000 patients with advanced cancer to identify T cell receptors shared across multiple patient populations. T cells carry these receptors on their cell membranes to recognize specific tumor antigens. Scientists study them to build targeted cancer immunotherapies.

Discovering new receptors typically requires labor-intensive workflows and difficult-to-acquire tissue specimens. Emily Jackson and her research team bypassed those hurdles by examining public datasets from large patient cohorts. Their pipeline combed through 26 million unique T cell receptor chains.

Analytical Pipeline Flags Receptors Tied to Common Cancer Antigens

The analytical pipeline flagged receptors tied to common cancer antigens, including human papillomavirus proteins and the mutated KRAS protein. T cells drive cellular immunity by targeting infected or malignant cells after recognizing foreign antigens presented on major histocompatibility complex molecules. Most T cells express alpha and beta chains that rely on these MHC proteins.

Only 1% to 5% of T cells express gamma and delta chains. Those specialized cells are not MHC restricted and participate in innate immune responses, though it remains unclear which exact ligands they bind. The team focused on the predominant alpha and beta heterodimeric surface receptors.

Eleven Receptor Families Shared Across Advanced Cancers

The study characterized 11 families of T cell receptors found across patients with more than 30 different types of advanced cancer. Nine of those receptor families were previously unknown. The variable region of each receptor is assembled through V(D)J recombination, where variable, diversity, and joining gene segments combine.

That recombination generates immense diversity among the receptors. By looking across routine clinical testing data, the researchers captured immune repertoires that remained largely untapped. The American Association for the Advancement of Science published the findings in Science Translational Medicine.

Questions Remaining About Ligand Binding and Rare Receptors

Researchers still do not know which exact ligands are bound by gamma and delta T cell chains.

Frequently Asked Questions

How many patients were included in the genomic dataset?

The database compiled genomic and clinical data from more than 150,000 patients suffering from over 30 distinct types of advanced cancer.

What specific antigens did the analytical pipeline detect?

The method identified receptors associated with frequent cancer antigens, including human papillomavirus proteins and mutated KRAS protein.

Where was the study published?

The findings appeared in the journal Science Translational Medicine following research led by Emily Jackson and her colleagues.