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 for inhibiting an autoimmune disease by administering to a subject a therapeutically effective amount of a composition that induces conversion of naive T cells into Foxp3+ regulatory T cells to induce immunosuppression in the subject. Methods for detecting in a subject an autoimmune disease or a predisposition to a autoimmune disease, and methods for assessing the efficacy of a therapy for an autoimmune disease, particularly type 1 diabetes.

Methods for determination of risk, previous history and/or presence of a betaretrovirus infection in a subject are described herein. Said methods may comprise incubating a biological sample from the subject, the biological sample comprising immune effector-producing cells, with one or more betaretrovirus-specific epitopes, the betaretrovirus-specific epitopes comprising at least 7 contiguous amino acids according to any one of SEQ ID Nos. 1-36, and measuring the production of immune effectors by the immune effector-producing cells, wherein production of the immune effectors by the immune effector-producing cells determines risk and/or presence of betaretrovirus infection in the subject. Isolated peptides and kits for carrying out the methods are also described.

Disclosed are methods of isolating a TCR having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous APCs of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; selecting the autologous T cells; and isolating a nucleotide sequence that encodes the TCR from the selected autologous T cells, wherein the TCR has antigenic specificity for the mutated amino acid sequence encoded by the cancer-specific mutation. Also disclosed are related methods of preparing a population of cells, populations of cells, TCRs, pharmaceutical compositions, and methods of treating or preventing cancer.

Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Programmed cell death 1 (Pdcd1) gene. The non-human animals, in some embodiments, comprise a genetic modification to an endogenous Pdcd1 gene so that the non-human animals express a PD-1 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

Methods of selecting test compounds on the basis of their cellular response profiles are disclosed. For a given test compound, a cellular response is determined by introducing into an array of individually addressable microwells a population of cells comprising a plurality of cell types and contacting the cells with the test compound. The cellular response profile for the test compound is then compared to a desired cellular response profile, and the test compound is selected based on the comparison.

An in vitro or ex vivo method, based on the measurement of the expression of cytokine(s), from a patient's blood sample, incubated with a stimulus, for determining the risk of occurrence of a healthcare-associated infection in the patient, within seven days following the day on which the collection of the biological sample has been performed from the patient.

The invention provides methods, kits and reagents for diagnosing fibromyalgia (FM) in an individual by determining whether the levels of one or more cytokines in the individual are altered, as compared to control levels. The altered level(s) or patterns of expression of the cytokines measured in the affected individual compared to the level from the control is predictive/indicative of FM in the individual.

The present invention relates to a method for real-time measurement of the secretion of at least one compound by at least one individual cell, comprising: the culturing, in a liquid medium, of at least one cell in a culture chamber, at least one wall of which comprises at least one sensitive area, a sensitive area comprising a plurality of ligands, attached to a solid support, each ligand being able to bind specifically to the compound, and an element for real-time transduction of a signal produced by the binding of the compound to one of the ligands; the identification, in a sensitive area, of at least one spot producing a signal; the real-time measurement of the signal produced by the spot identified, representing the amount of compound secreted by an individual cell.

The present inventors have identified specific oncogenic pathways preferentially activated in BRAF-mutated-melanoma cells and a pathway pattern that predicts resistance of BRAF-mutated melanoma to BRAF/MEK inhibitors, providing novel clinical implications for melanoma therapy. In one embodiment, a method comprises (a) testing a sample oiBRAF-mutated melanoma cells isolated from a patient and measuring the expression levels of genes expressed in the following oncogenic pathways: TNFa, EGFR, IFNa, hypoxia, IFNy, STAT3 and Myc; (b) calculating a 7-pathway activation pattern based on the measured expression levels of step (a); and (c) identifying the patient's resistance level to BRAF/MEK inhibitor treatment based on comparison of the calculated 7-pathway activation pattern to a reference.