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.

The present disclosure provides a method of treating cancer by immune checkpoint blockade, or selecting patients for treatment with immune checkpoint blockers, by detecting tumors with high levels of T-lymphocytes with low levels of activation and proliferation. In various embodiments the tissue sample may be from a conventional biopsy. In various embodiments the cancer may be non-small cell lung cancer.

Methods for treating inflammatory skin conditions, such as atopic dermatitis and psoriasis, and for promoting skin wound healing and for treating skin wounds, such as thermal and pressure injury, by reducing the activity of Granzyme K.

The present invention relates to the field of treatment efficacy prediction in patients with malignant diseases. More precisely, this invention relates to the prediction of the efficacy of a treatment in cancer patients, based on the precise quantification of several biological markers that are related to the innate and adaptive immune response of said patient against said cancer.

The disclosure provides methods of determining patient populations amenable or suitable for immunomodulatory treatment of disease such as cancer by measuring the relative or absolute levels of T-cell sub-populations correlated with disease such as cancer.

Methods are provided to separately isolate antigen-binding T cells and antigen-activated T cells derived from a starting population of peripheral blood mononuclear cells, and to identify overlapping T cell receptor clonotypes. Antigens include personal and shared neoantigens as well as cancer-testis antigens. The T cell receptor clonotypes can be further used to develop cancer treatment therapies.

The disclosure provides methods of determining patient populations amenable or suitable for immunomodulatory treatment of disease such as cancer by measuring the relative or absolute levels of T-cell sub-populations correlated with disease such as cancer.

Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell.

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.

In one aspect, provided herein is a method comprising: (a) (i) determining cytolytic activity in a tumor from the subject; and/or (ii) determining genetic alterations associated with cytolytic activity in the tumor; and (b) administering an immunotherapeutic agent to the subject if (i) cytolytic activity is detected in the tumor and/or (ii) a genetic alteration associated with induction of cytolytic activity, tumor resistance to cytolytic activity and/or suppression of cytolytic activity is detected in the tumor.