This document provides methods and materials involved in treating autoimmune conditions. For example, methods and materials for using either (a) one or more tumor necrosis factor alpha (TNF-) inhibitors or (b) one or more Janus kinase (JAK) inhibitors to treat autoimmune conditions such as rheumatoid arthritis are provided.

Disclosed herein are methods in which an individual with multiple sclerosis (MS) can be classified into one of six subject groups, each subject group predictive for the patient's responsiveness to an interferon- (IFN-) therapy. The individual with MS can be classified according to the individual's serum marker levels, e.g., at baseline or following treatment with therapy. Depending on the classification, the individual with MS can be treated with standard therapies (e.g. IFN-) or one or more alternative therapies with or without IFN-.

Provided are methods for treating cancer by converting tumor-resident macrophages into a hybrid M1/M2 macrophage phenotype; this phenotype has attributes that are advantageous for cancer therapy. Hybrid markers include (lower than M2, higher than M1): SPP1, CD209, and CD206, and induced markers include MERTK, C1QC, IFNa, IFNb, CXCL10, 4-1BBL, and MYC. The methods include administering a therapeutic that effects the phenotypic conversion. Therapeutics, such as delivery vehicles, including immunostimulatory bacteria with genome modifications, are designed so that they do not induce or result in a sufficient TLR2, TLR4, TLR5 response to inhibit type I IFN. The therapeutics also encode a payload that encodes immunostimulatory proteins, such as a cytokine and a modified cytosolic DNA/RNA sensor that constitutively induces type I IFN, such as a modified STING protein. The combination of payload immunostimulatory proteins and properties of the therapeutic delivery vehicle, upon administration, results in macrophage with the hybrid phenotype. The therapeutics are administered to subjects identified as having tumors that comprise proliferating M2 macrophages.

Compositions and methods are provided for classification of individuals suffering from a demyelinating disease into groups that are informative of the individual's responsiveness or lack of responsiveness to treatment with a J3-interferon (IFNJ3) acting therapy. In particular, it is shown that the effective immunomodulatory treatment of demyelinating disease with IFNJ3 is associated with an increase in circulating transitional B cells in the patient. Diseases of interest include without limitation inflammatory demyelinating diseases of the central nervous system, e.g. multiple sclerosis, neuromyelitis optica (NMO), experimental autoimmune encephalitis (EAE), acute disseminated encephalomyelitis (ADEM), etc.

There is described herein a method for predicting response to anti-PD1 based therapy in a subject with cancer, the method comprising: providing a sample of peripheral blood from the subject; adding an IFN-I to the sample; assessing T-cell response to IFN-I stimulation in the peripheral blood sample by measuring the expression of IFN-I stimulated genes; and predicting a better outcome in response to anti-PD1 therapy if the assessment in the previous step indicates T-cell resistance to IFN-I stimulation and predicting a poorer outcome in response to anti-PD1 therapy if the assessment step indicates T-cell responsiveness to IFN-I stimulation.

The present invention relates to combination therapies useful for the treatment of cancer. In particular, the invention relates to a therapeutic combination which comprises a PD-1 antagonist, an ATR inhibitor and a platinating agent.

The disclosure relates to methods and assay that assists in the diagnosis of autoimmune and chronic inflammatory disorders such as systemic lupus erythematosus and rheumatoid arthritis by analyzing drug-responsiveness of an interferon signal in a hematological sample (e.g., blood) obtained from a human subject. The assay involves comparing the interferon signal in a control aliquot of the sample with the same interferon sample in an aliquot that has been exposed to a therapeutic modality (e.g., combined with a drug) that is known to be efficacious to treat the disorder. A significant difference between the interferon signals of the control and treated aliquots that corresponds to a characteristic interferon signature for the disorder indicates that the subject is afflicted with, or is likely to develop, the disorder.