Methods are disclosed for treating a subject with a tumor. These methods include administering to the subject a therapeutically effective amount of CD8.sup.+CD39.sup.+CD103.sup.+ T cells. Methods also are disclosed for isolating a nucleic acid encoding a T cell receptor (TCR) that specifically binds a tumor cell antigen. These methods include isolating CD8.sup.+CD39.sup.+CD103.sup.+ T cells from a sample from a subject with a tumor expressing the tumor cell antigen, and cloning a nucleic acid molecule encoding a TCR from the CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In addition, methods are disclosed for expanding CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In additional embodiments, methods are disclosed for determining if a subject with a tumor will respond to a checkpoint inhibitor. The methods include detecting the presence of CD8.sup.+CD39.sup.+CD103.sup.+ T cells in a biological sample from a subject.

The present invention provides an in vitro method for the prognosis of disease progression in a patient that suffers from or is at risk of developing a solid tumor, said method comprising determining, in one or more samples from said patient, at least one of intratumoral infiltration by macrophages, and/or proximity of lymphocytes to tumor cells, and/or proximity of macrophages to tumor cells, and/or presence or absence of one or more nearby tertiary lymphoid structures (TLS), and an anti-angiogenic drug, optionally combined with an immune checkpoint inhibitor, for use in the treatment of such patient.

The present invention relates to the field of tumor immunology. It provides a method for identifying mutation-related human CD8+ T cells, in particular, tumor-specific T cells of a human subject, comprising analyzing CD8+ T cells of the subject by analysing the expression of at least one marker selected from a first group consisting of CD82, CD194, CD244, CD28, CD62L and CD55, and preferably, a marker selected from a second group comprising CD11a or CD18 or CD43. A preferred marker for mutation-related CD8+ T cells is CD82, which may be analysed in combination, e.g., with CD11a. Without the need to identify any epitope to which T cells reacts, this method can advantageously be used to isolate the entire individual pool of mutation-related T cells, and, optionally, to identify the sequence of a mutation-related TCR, which allows for generation of transgenic T cells expressing the TCR. Compositions substantially comprising tumor-specific CD82.sup.hiCD8+ T cells and/or CD194.sup.hi, CD244.sup.−, CD28.sup.+, CD62L.sup.+ and/or CD55.sup.+ CD82.sup.hi CD8+ T cells can be used for treatment of a cancer patient, e.g., by adoptive T cell transfer. The method of the invention can also be used for diagnostic purposes to identify human mutation-related T cells or diagnosing a tumor disease or for testing responses of a cancer patient to an immune stimulatory therapy, preferably, a therapy with a checkpoint inhibitor.

Methods are disclosed for treating a subject with a tumor. These methods include administering to the subject a therapeutically effective amount of CD8.sup.+CD39.sup.+CD103.sup.+ T cells. Methods also are disclosed for isolating a nucleic acid encoding a T cell receptor (TCR) that specifically binds a tumor cell antigen. These methods include isolating CD8.sup.+CD39.sup.+CD103.sup.+ T cells from a sample from a subject with a tumor expressing the tumor cell antigen, and cloning a nucleic acid molecule encoding a TCR from the CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In addition, methods are disclosed for expanding CD8.sup.+CD39.sup.+CD103.sup.+ T cells. In additional embodiments, methods are disclosed for determining if a subject with a tumor will respond to a checkpoint inhibitor. The methods include detecting the presence of CD8.sup.+CD39.sup.+CD103.sup.+ T cells in a biological sample from a subject.

The present invention relates to a method for diagnosis of delayed bone fracture healing, comprising determining the frequency of a subpopulation of CD8+ cells selected from a first group comprised of CD8+CD57+, CD8+CD28− and CD8+CD28−/CD57+, in a sample obtained from a subject. The present invention further relates to a system and a kit of parts for prediction and resulting options for preventing of delayed bone fracture healing.

The present disclosure relates in some aspects to methods, cells, and compositions for preparing cells and compositions for genetic engineering and cell therapy. Provided in some embodiments are streamlined cell preparation methods, e.g., for isolation, processing, incubation, and genetic engineering of cells and populations of cells. Also provided are cells and compositions produced by the methods and methods of their use. The cells can include immune cells, such as T cells, and generally include a plurality of isolated T cell populations or types. In some aspects, the methods arc capable of preparing of a plurality of different cell populations for adoptive therapy using fewer steps and/or resources and/or reduced handling compared with other methods.

The present invention provides a method for determining the clinical prognosis of a human subject to the administration of a pharmaceutical composition comprising of stem cells (preferably mesenchymal stem cells), stromal cells, regulatory T-cells, fibroblasts and combinations thereof.

Provided relates to the field of cytometry, specifically to flow cytometric methods and kits for improved diagnosis, prognosis and monitoring of tumors and other lesions involving immune cell infiltration. Further provided are embodiments of the subject matter which relate to compositions and methods providing high resolution quantitative means for immunophenotyping and immune modeling, and for identification of disease prognostic and therapy predictive biomarkers.

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.

This disclosure relates to methods for enriching a first population of cells positive for a target moiety and/or a second population of cells positive for the target moiety from a sample, wherein a level of the target moiety among the first population of cells is relatively lower than the level of the target moiety among the second population of cells. The methods of this disclosure may also be adapted to assays for determining distinct populations of cells positive for a target moiety in a sample, and to assays for optimizing enrichment conditions. Last, this disclosure relates to kits of components that may be used to carry out the methods and assays.