The present invention relates to compositions and methods for identifying, assessing, preventing, and treating melanoma. A variety of PD-L1 isoform biomarkers are provided, wherein alterations in the copy number of one or more of the biomarkers and/or alterations in the amount, structure, and/or activity of one or more of the biomarkers is associated with melanoma status.

An assay measuring protease mediated degradation of type IV collagen and its biomarker potential for identifying cancer patients with a T-cell permissive tumor microenvironment is described.

The present invention relates to compositions and methods for binding and inhibiting renalase. In one embodiment, the renalase binding molecule inhibits renalase activity. Thus, in diseases and conditions where a reduction of renalase activity is beneficial, such inhibitory renalase binding molecules may act as therapeutics.

Disclosed herein are methods for using therapeutic compounds, for example BH3 mimetics such as MCL1 inhibitors, to treat patients that may have failed to respond to targeted or immunotherapy treatments. In several embodiments, methods for treating such patients include combining MCL1 inhibitors with immunotherapies to enhance immunotherapy treatment. For example, the combination of MCL1 inhibitors with immunotherapies is used to treat cancer, such as melanoma. In some embodiments, MCL1 inhibitory compounds and therapies may be useful in treating tissues or tumors having one or more MDSC cell expressing high levels of MCL1. In some embodiments, MCL1 and BCL2 inhibitory compounds and therapies comprising same may be used to treat one or more melanomas, for example cutaneous melanoma, melanoma subtypes selected from uveal, acral, and mucosal. In some embodiments, MCL1 inhibitory compounds and therapies comprising same may be used to treat one or more melanomas, for example uveal melanoma. In many embodiments the targeted cells or tissues may not have BRAF mutations.

Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, tumor infiltrating lymphocytes (TILs) are identified that can be used with adoptive cell transfer to target, penetrate, and kill solid tumor masses. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed TILs.

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

Described herein are methods for stratifying and evaluating melanoma treatment response in a subject using single cell RNA sequencing (scRNA-seq) and a two-step deconvolution analysis and optionally administering a treatment depending on the results. Embodiment described herein are methods for stratifying and evaluating melanoma treatment response in a subject based on single cell or bulk RNA sequencing, bulk transcriptome profiling and/or transcript counting and a two-step deconvolution analysis and optionally administering a treatment depending on the results.

The present invention relates to autoantibody biomarkers associated with melanoma. The autoantibody biomarkers can be used to detect or diagnose melanoma and can also be used to inform treatment of melanoma patients, particularly treatment with checkpoint inhibitors. The autoantibody biomarkers can be used in a variety of methods including: methods of selecting melanoma patients for treatment; methods of predicting responsiveness to treatment; methods of predicting survival responsive to treatment; and methods of predicting the risk of immune-related adverse events (irAEs) in patients treated with checkpoint inhibitors.

Provided is a technique of predicting prognosis of skin cancer. A method for prognosis prediction of skin cancer includes: a step of obtaining a correlation amount correlated with an expression level of a glucose-6-phosphate dehydrogenase in a sample collected from a patient with the skin cancer; and a step of determining that the prognosis of the skin cancer is poorer when the correlation amount is large than that when the correlation amount is small.

Provided herein are predictive biomarker signatures that identify patients as likely to benefit from TIL therapy. Also provided are tumor immunotherapy resistance pathways that may be targets of combination therapies to enhance TIL therapy.