Method of Treating Cancer

A method of treating breast cancer in a subject in need thereof, comprising:

• administering to the subject an immune checkpoint inhibitor that blocks programmed cell death protein-1 (PD-1) or programmed death-ligand 1 (PD-L1);
• and
• administering to the subject a fecal microbiota transplantation (FMT) composition obtained from a post-bariatric surgery human donor who has undergone bariatric surgery at least three months prior to donation and achieved at least a 10% reduction in body weight relative to pre-surgical weight,
• wherein the FMT composition is characterized by enrichment of order Clostridiales, including family Peptostreptococcaceae, relative to obese non-surgical controls, and wherein the FMT composition increases circulating branched-chain amino acid (BCAA) levels and invariant natural killer T (iNKT) cell activation within the tumor microenvironment of the subject relative to pre-treatment baseline,
• thereby improving the therapeutic response of the subject to the immune checkpoint inhibitor.

A method of augmenting immune checkpoint blockade therapy in a subject with a solid tumor, comprising:

• administering to the subject an immune checkpoint inhibitor that blocks programmed cell death protein-1 (PD-1) or programmed death-ligand 1 (PD-L1);
• and
• administering to the subject an effective amount of branched-chain amino acids (BCAAs) comprising leucine, isoleucine, and valine sufficient to increase circulating BCAA plasma concentration by at least 10% relative to pre-treatment baseline, thereby activating iNKT1 cells within the tumor microenvironment and improving a therapeutic response to the immune checkpoint inhibitor,
• wherein the solid tumor is breast cancer, triple-negative breast cancer, colorectal cancer, melanoma, or another solid tumor in which iNKT1 cell activation within the tumor microenvironment is associated with anti-tumor immune response.