Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: Described herein are methods and computer systems for classification of CD8 T-cell topology using artificial intelligence and machine learning. A plurality of histology images of tissue samples in a plurality of patients are received by a computer system. An image analysis of the plurality of histology images is performed to obtain a CD8+ T-cell abundance in the tumor parenchyma and stroma in each of the plurality of histology images. A machine learning algorithm is then trained using results of the image analysis and the CD8+ T-cell abundance in the tumor parenchyma and stroma. Based on the training, a machine learning feature space comprising a plurality of classifications is generated, and boundaries between the plurality of classifications in the machine learning feature space are identified.

Abstract: The present disclosure provides methods of identifying a subject suitable for an anti-PD-?PD-L1 antagonist therapy comprising measuring assay CD8 localization and PD-L1 expression in a tumor sample obtained from the subject. In some aspects, method further comprises administering (i) an anti-PD-?PD-L1 antagonist therapy or (ii) an anti-PD-?PD-L1 antagonist and anti-CT-LA-4 antagonist combination therapy to a subject identified as having a tumor exhibiting an excluded CD8 localization phenotype, wherein the tumor is PD-L1 negative.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.

Abstract: The disclosure provides LAG-3 antagonists and methods comprising the same for treating a cancer in a subject based on a LAG-3 density score and/or a LAG-3 proportion score in a tumor sample from the subject. The disclosure also provides methods of identifying a subject responsive to a LAG-3 antagonist therapy.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine/Threonine Kinase 11 (STK11), or both PD-L1 and STK11.

Abstract: The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-Ll positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine/Threonine Kinase 11 (STK11), or both PD-L1 and STK11.

Abstract: This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1. In some embodiments, the subject carries a wild-type STK11 gene.