Detecting cancer

A method of treating a subject determined to be at risk for having a progressing or high-grade pre-invasive lesion, nodule or small mass, or having a solid malignant tumour, the method comprising:

• analysing a proportion of T cells in a sample of blood obtained from the subject which are activated and/or exhausted T cells by analysing a trait of the T cells, wherein the trait is a phenotypic trait, and wherein the analysing comprises:
• determining a diversity or clonality of T cells in the sample of blood obtained from the subject, wherein the subject is at risk if
• (i) the diversity of a repertoire of T cell receptors (TCRs) is lower than a diversity of the repertoire of TCRs of a comparison subject or a plurality of comparison subjects,
• ii) a D50 diversity score is lower than a D50 diversity score obtained from analysing T cells in a sample of blood obtained from a comparison subject or a plurality of comparison subjects,
• iii) a clonality score is higher than a clonality score obtained from analysing T cells in a sample of blood obtained from a comparison subject or a plurality of comparison subjects,
• iv) a Hill number is lower than a Hill number obtained from analysing T cells in a sample of blood obtained from a comparison subject or a plurality of comparison subjects,
• v) a clonality of a repertoire of TCRs occupied by the top n clones is higher than a clonality of a repertoire of TCRs occupied by the top n clones in a comparison subject or a plurality of comparison subjects, wherein n is between 50 and 1000, or
• vi) a proportion of a repertoire of TCRs occupied by small clones is lower than a proportion of a repertoire of TCRs occupied by small clones in a comparison subject or a plurality of comparison subjects,
• vii) a proportion of a repertoire of TCRs occupied by large clones is higher than a proportion of a repertoire of TCRs occupied by large clones in a comparison subject or a plurality of comparison subjects, or
• viii) a ratio of a repertoire of TCRs occupied by large clones:small clones is higher than a ratio of a repertoire of TCRs occupied by large clones:small clones in a comparison subject or a plurality of comparison subjects;
• determining the subject is at risk for having a progressing or high-grade pre-invasive lesion, nodule or small mass, or having a solid malignant tumour;
• and
• treating the subject based on the determination that the subject is at risk.