IMMUNOCOMPETENCE ASSESSMENT BY ADAPTIVE IMMUNE RECEPTOR DIVERSITY AND CLONALITY CHARACTERIZATION

摘要

Disclosed are methods for determining the immunological status of the adaptive immune system of a subject by identifying and quantifying rearranged DNA (and/or subsequently transcribed RNA) sequences encoding T cell receptor (TCR) and/or immunoglobulin (IG) polypeptides, in a lymphoid DNA-containing sample from the subject. TCR and/or IG sequence diversity and sequence distribution permit immunocompetence and immune repertoire assessment and reflect the degree of T cell or B cell clonality and clonal expansion in the sample. Methods for stratifying patient populations on the basis of immunocompetence including likelihood of responding to immunotherapy are also described.

主权项

1. A method for predicting an immunological response of a test subject to an immunotherapy, comprising:
amplifying a plurality of nucleic acid sequences from one or more solid tumor tissue samples obtained from a test subject at one or more time points prior to and after treatment with said immunotherapy comprising lymphoid cells from a test subject in a multiplex PCR assay using a plurality of adaptive immune receptor (AIR) V-segment oligonucleotide primers and either a plurality of AIR J-segment oligonucleotide primers or one or more AIR C-segment oligonucleotide primers to obtain a plurality of AIR amplicons; sequencing said AIR amplicons to obtain nucleic acid sequence information; determining a test subject immunological rating score for said one or more solid tumor tissue samples by quantifying said nucleic acid sequence information; comparing said test subject immunological rating score with a set of immunological rating scores of subjects with known responses to said immunotherapy; and predicting an immunological response for said test subject to said immunotherapy based on said comparison.