Abstract: Methods of predicting or detecting sensitivity to therapeutic effects of anti-PD-1 therapy in a patient suffering from melanoma, as well as for selecting somatic mutanomes and transcriptomes of melanoma biopsies. A tumor sample obtained from the patient is assayed for a measure of anti-PD-1 therapy sensitivity via, for example, whole transcriptome sequencing, antibody based protein quantifications, mass spectrometry based protein quantification, targeted mRNA sequencing, real-time RT-PCR, Sanger sequencing, targeted sequencing and/or whole exome/genome sequencing. Samples are selected that exhibit a higher first enrichment similarity score and/or a lower second enrichment similarity score, and/or at least one measure of sensitivity. A patient whose sample was selected herein as a candidate for anti-PD-1 therapy is thereby identified. The method of the invention can further comprise treating the patient with anti-PD-1 therapy, optionally in conjunction with combinatorial therapy.

Abstract: Disclosed herein are methods of treating or assessing cancer in a subject wherein it has been determined whether the cancer comprises a loss of function mutation or disruption in an immune pathway. The loss of function mutation or disruption can be in JAK1 or JAK2. The loss of function mutation or disruption can be in B2M. The methods can include administering an immune checkpoint therapy such as anti-PD1 or anti-PDL1. The methods can include administering an alternative therapy to an immune checkpoint therapy. In some aspects, the method includes determining whether the cancer comprises a loss of function mutation or disruption in an immune pathway.

Abstract: Methods of predicting or detecting sensitivity to therapeutic effects of anti-PD-1 therapy in a patient suffering from melanoma, as well as for selecting somatic mutanomes and transcriptomes of melanoma biopsies. A tumor sample obtained from the patient is assayed for a measure of anti-PD-1 therapy sensitivity via, for example, whole transcriptome sequencing, antibody based protein quantifications, mass spectrometry based protein quantification, targeted mRNA sequencing, real-time RT-PCR, Sanger sequencing, targeted sequencing and/or whole exome/genome sequencing. Samples are selected that exhibit a higher first enrichment similarity score and/or a lower second enrichment similarity score, and/or at least one measure of sensitivity. A patient whose sample was selected herein as a candidate for anti-PD-1 therapy is thereby identified. The method of the invention can further comprise treating the patient with anti-PD-1 therapy, optionally in conjunction with combinatorial therapy.

Abstract: Disclosed herein are methods of treating or assessing cancer in a subject wherein it has been determined whether the cancer comprises a loss of function mutation or disruption in an immune pathway. The loss of function mutation or disruption can be in JAK1 or JAK2. The loss of function mutation or disruption can be in B2M. The methods can include administering an immune checkpoint therapy such as anti-PD1 or anti-PDL1. The methods can include administering an alternative therapy to an immune checkpoint therapy. In some aspects, the method includes determining whether the cancer comprises a loss of function mutation or disruption in an immune pathway.