Abstract: A method for determining whether a subject is at risk for having a progressing or high-grade pre-invasive lesion, nodule or small mass, or having a solid malignant tumour is described the method comprising: (i) determining a ratio of activated and/or exhausted T cells:naive and/or resting T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence or absence of a panel of biomarkers comprising Ki67 and CD39, or (ii) determining a ratio of activated and/or exhausted T cells:T cells which are not activated and/or exhausted T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using cytometry to detect the presence or absence of a panel of biomarkers comprising Ki67 and CD39, (iii) determining a proportion of activated and/or exhausted T cells as a percentage of T cells in a sample of blood obtained from the subject, wherein the determining comprises analysing T cells using

Abstract: A method for determining whether a subject is at risk for having a progressing or high-grade pre-invasive lesion, nodule or small mass, or having a solid malignant tumour is described. The method involves analysing the 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, e.g., via analysing biomarker expression using cytometry. In some instances, a plurality of traits is analysed and combined, e.g., via analysing biomarker expression using cytometry in combination with analysing the diversity or clonality of the blood TCR repertoire using TCR-seq.

Abstract: The present invention provides an engineered T cell for use in a method of treatment of a proliferative disorder, wherein the engineered T cell has modulated expression of one or more genes selected from SIT1, SAMSN1, SIRPG, CD7, CD82, FCRL3, IL1RAP, FURIN, STOM, AXL, E2F1, C5ORF30, CLDND1, COTL1, DUSP4, EPHA1, FABP5, GFI1, ITM2A, PARK7, PECAM1, PHLDA1, RAB27A, RBPJ, RGS1, RGS2, RNASEH2A, SUV39H1, and TNIP3. Further provided are activity modulators of one or more proteins encoded by genes selected from SIT1, SAMSN1, SIRPG, CD7, CD82, FCRL3, IL1RAP, FURIN, STOM, AXL, E2F1, C5ORF30, CLDND1, COTL1, DUSP4, EPHA1, FABP5, GFI1, ITM2A, PARK7, PECAM1, PHLDA1, RAB27A, RBPJ, RGS1, RGS2, RNASEH2A, SUV39H1, and TNIP3 for use in a method of enhancing immunotherapy in a subject having a proliferative disorder. Also provided are related methods of treatment employing the engineered T cell and/or inhibitor.

Abstract: The invention is generally directed to a method of enhancing proliferation of T regulatory cells (Tregs) in vitro, comprising contacting Tregs with cells (I), or conditioned medium from the cells, in the presence of one or more Treg stimulation agents. The Treg stimulation agent(s) is present in an amount and for a time effective to stimulate proliferation of the Tregs. The cells (I) are present in an amount and for a time effective to enhance proliferation of the Tregs. The cells (I) are non-embryonic stem, non-germ cells characterized by one or more of the following: extended replication in culture and express markers of extended replication, express markers of pluripotentiality, and have broad differentiation potential, are not tumorigenic or transformed, and have a normal karyotype. The invention is also directed to methods for immune modulation using the proliferated Tregs, cell banks, drug discovery methods, populations, and compositions of the proliferated Tregs.