Provided herein are methods and compositions related to the selection T cells and/or subjects for adoptive immunotherapy based on the expression of one or more biomarkers.

Methods are described for identifying CDI patients as well as CDI patients at risk for recurrence. Embodiments include: (1) flow cytometry of circulating peripheral blood mononuclear cells (PBMC) to phenotype for the less efficient immunoglobulin response to bacterial toxins and surface antigens that characterizes patients who will become recurrent; (2) stratification by means of complete blood count (CBC) using a Coulter counter to detect the differences in lower angle light scatter (LAL), which has a larger range in the recurrent population; and (3) stratification by means of complete blood count (CBC) using a Coulter counter to detect the lower axial light loss (AL2) exhibited in recurrent patients.

The present invention provides biomarkers for use in determining populations for treatment with anti-PVRIG antibodies and such biomarkers include, for example PVRIG and/or PVRL2 expression.

There is provided methods of determining tuberculosis (TB) infection status in an individual comprising: (i) providing a sample comprising T-cells; (ii) exposing the sample of (i) to one or more TB antigens; (iii) identifying T-cells in the sample that are CD4 positive and (a) secrete TNF-α without secreting IFN-γ; or (b) secrete IFN-γ without secreting TNF-α; (iv) identifying those cells of (iii) which are also CCR7 and, CD127 negative; and optionally (v) calculating the cells identified in (iv) as a percentage of those identified in (iii); wherein the identification of cells in (iv) and/or the percentage of T-cells calculated in (v) correlates to TB infection status of the individual, and wherein steps (iii) and (iv) can be carried out either sequentially or simultaneously. There are also provided compositions and kits for use in such methods.

Provided herein are compositions and methods for the treatment of cancer by inhibition of β-catenin or a β-catenin pathway. In particular, inhibitors of β-catenin and/or the Wnt/β-catenin signaling pathway are employed prevent or reverse evasion of immune response or immunotherapy by cancers.

Provided are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for predicting likelihood of the subject responding to a therapy, such as a cell therapy, e.g., a chimeric antigen receptor (CAR) T cell therapy. In some aspects, the predicting is based on detecting certain biomarkers of immune cells associated with and/or that correlate with response following administration of the therapy. The methods generally involve detecting a marker by assaying a biological sample from a subject that is a candidate for treatment, optionally with a cell therapy, to determine if the subject is likely to respond to the therapy. The present disclosure also provides methods for treating a subject having a disease or condition, in some cases involving administration of the cell therapy, based on assessment the biomarker. Also provided herein are reagents and kits for performing the methods.

The present invention provides novel pan-cancer T cell exhaustion regulators. CXCR6 expressed in CD8+ T cells was specifically identified as regulating anti-tumor immunity. Modulating CXCR6-CXCL16 interaction is useful in modulating anti-tumor immunity. The identified genes may be modulated in T cells for use in adoptive cell transfer. The identified genes may be modulated in vivo.

The present invention relates to methods for enhancing the potency of the immune checkpoint inhibitors. In particular, the present invention relates to a method for enhancing the potency of an immune checkpoint inhibitor administered to a subject as part of a treatment regimen, the method comprising administering a pharmaceutically effective amount of a SK1 inhibitor to a subject in combination with the immune checkpoint inhibitor.

The present invention provides a method of obtaining information for the diagnosis or treatment, mainly of cancer or an immune system-related disease, the method including the step of quantifying the expression level of a cancer-associated protein or a nucleic acid in a tumor cell; and/or the step of quantifying the expression level of a protein or a nucleic acid in an immune cell, using a specimen derived from tumor tissue of a human or a non-human.

The present invention provides methods of preventing, reversing or increasing T cell exhaustion in a patient having a disease. The present invention also provides methods for treating a disease in a patient having the disease. The present invention also provides an engineered T cell comprising a high priority epigenetic pathway that has been targeted, and uses thereof.