Predicting patient responsiveness to immune checkpoint inhibitors

A method of predicting clinical response of a patient to treatment of a cancer by a CTLA-4 inhibitor, the method comprising the steps of:

• (a) generating a first clonotype profile from recombined T cell receptor genes or nucleic acids transcribed therefrom from a first patient sample taken before treatment by a CTLA-4 inhibitor;
• (b) generating a second clonotype profile from recombined T cell receptor genes or nucleic acids transcribed therefrom from a second patient sample taken during or after treatment by a CTLA-4 inhibitor;
• (c) determining a number of clonotypes that decrease in frequency between the first and second clonotype profiles;
• and
• (d) predicting a lack of responsiveness in the patient to the treatment whenever the number of clonotypes that decrease in frequency is greater than a predetermined value.

A method of selecting a patient having a cancer for treatment by a CTLA-4 inhibitor, the method comprising the steps of:

• (a) generating a first clonotype profile from recombined T cell receptor genes or nucleic acids transcribed therefrom from a first patient sample taken before treatment by a CTLA-4 inhibitor;
• (b) generating a second clonotype profile from recombined T cell receptor genes or nucleic acids transcribed therefrom from a second patient sample taken during or after treatment by a CTLA-4 inhibitor;
• (c) determining a number of clonotypes that decrease in frequency between the first and second clonotype profiles;
• and
• (d) selecting the patient for treatment with a CTLA-4 inhibitor whenever the number of clonotypes that decrease in frequency is below a predetermined value.