Provided are methods and compositions for a combination therapy for liver disorders such as hepatocellular carcinoma. Also provided is a method for determining the effectiveness of therapy involving tyrosine kinase inhibitors such as sorafenib. The method comprises determining the status of PD-1 on T cells, and based on a change in the level of PD-1 on certain cells, a determination of the effectiveness of the tyrosine kinase, and an indication for a combination therapy comprising a lower dose of tyrosine kinase inhibitor and a PD-1 inhibitor can be made.

The present invention belongs to the fields of tumor therapy and molecular immunology, and provides an anti-CTLA4 monoclonal antibody or antigen binding fragment thereof, a pharmaceutical composition thereof and use thereof. The monoclonal antibody of the present invention can block the binding of CLTA4 to B7, relieve the immunosuppression on the body by CTLA4, and activate T lymphocytes.

The disclosure provides methods for the selection and isolation of T cells expressing programmed cell death 1 (PD-1) and for selecting a PD-1 expression level of the isolated PD-1 expressing T cells. The disclosure also provides methods of large scale expansion of selected and isolated PD-1 expressing T cells, as well as methods for treating a subject comprising administering selected and isolated PD-1 expressing T cells to the subject.

Methods for obtaining a tuberculosis assessment in a subject are provided. Aspects of the methods include assaying a tuberculosis (TB) activated sample from the subject for at least one of: (i) CD154.sup.+ T cells; and (ii) T cells having a central memory phenotype, such as a CM1 phenotype, CM2 phenotype or a CM3 phenotype; to obtain a TB biomarker signature, and then deriving a tuberculosis assessment for the subject from the TB biomarker signature. Aspects of the invention further include reagents, devices, systems, and kits thereof that find use in practicing the subject methods are provided. The methods and compositions find use in a variety of applications, including TB diagnosis and monitoring of TB treatment.

Variants of human PD-1 comprising one or more of amino acid substitutions in residues corresponding to N74, T76 and A132 of SEQ ID NO:1 are described. Also described are structures, obtained using X-ray crystallography, of the human PD-1/PD-L2 complex and mutant PD-1 variants. The structures of human PD-1 described in the present disclosure are useful in drug discovery, including small-molecule drug discovery. Accordingly, methods of using the structures in drug discovery are also described.

The present invention relates to a method for predicting the probability of having or developing a non-fusion, wherein said method comprises determining the frequency of a subpopulation of CD8+ T cells selected from CD8+CD57+, CD8+CD28 and CD8+CD57+CD28 in a sample obtained from a patient. The invention further relates to a system for predicting the probability of having or developing a non-fusion.

Embodiments of the present disclosure relate to methods for ex vivo determining whether a patient with metastatic melanoma is likely to benefit from a treatment with an anti CTLA-4 molecule, preferably ipilimumab, by analyzing the gut microbiota in a fecal sample from said patient.

An object of the present invention is to provide an effective method of predicting an effect of treatment by a PD-1/PD-L1 blockade, which is a method of predicting whether or not PD-1/PD-L1 blockade is effective for treatment of a subject suffering from a malignant tumor, which comprises detecting abnormality of genome relating to effectiveness of the PD-1/PD-L1 blockade in a tumor cell taken from the subject and evaluating the PD-1/PD-L1 blockade as useful for the treatment of the subject when there is the abnormality.

The invention provides methods of treating cancer and methods for selecting treatment approaches for cancer.

The present invention relates to anti-PD-1 antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease. These antibodies have CDRs as provided in the enclosed sequences. Also part of the invention are nucleic acids encoding these antibodies, expression vectors comprising such nucleotide sequences and host cells that comprise said nucleotide sequences or expression vectors.