Abstract: A microfluidic device is directed to sustaining a complex microbial community in direct and indirect contact with living human intestinal cells in vitro. The device includes a first microchannel having cultured cells of a human intestinal epithelium and microbiota, the first microchannel further having a first level of oxygen. The device further includes a second microchannel having cultured cells of a vascular endothelium, the second microchannel further having a second level of oxygen. The device also includes a membrane located at an interface region between the first microchannel and the second microchannel, the membrane being composed of an oxygen-permeable material or further having pores via which oxygen flows between the first microchannel and the second microchannel to form a physiologically-relevant oxygen gradient.

Abstract: A microfluidic device is directed to sustaining a complex microbial community in direct and indirect contact with living human intestinal cells in vitro. The device includes a first microchannel having cultured cells of a human intestinal epithelium and microbiota, the first microchannel further having a first level of oxygen. The device further includes a second microchannel having cultured cells of a vascular endothelium, the second microchannel further having a second level of oxygen. The device also includes a membrane located at an interface region between the first microchannel and the second microchannel, the membrane being composed of an oxygen-permeable material or further having pores via which oxygen flows between the first microchannel and the second microchannel to form a physiologically-relevant oxygen gradient.

Abstract: Provided herein are methods of treating cancer in an individual that has failed an anti-PD1/PD-L1 therapy, comprising selecting an individual that has failed a prior anti-PD1/PD-L1 therapy; and administering to the individual a first agent that blocks or disrupts PD-L2, RGMb, or a combination thereof, and a second agent that blocks or disrupts PD-L1, PD-1 or a combination thereof. Also provided herein are kits and therapeutic compositions for use in the methods described herein.

Abstract: Provided herein are methods and compositions for treating cancer or a tumor in a subject by administering to the subject a first agent that disrupts the interaction between PD-L2/RGMb and a second agent that disrupts the interaction between PD-1/PD-L1. The subject may have dysbiosis and/or be nonresponsive to immune checkpoint therapy.

Abstract: Provided herein are methods and compositions for treating cancer or a tumor in a subject by administering to the subject a first agent that disrupts the interaction between PD-L2/RGMb and a second agent that disrupts the interaction between PD-1/PD-L1. The subject may have dysbiosis and/or be nonresponsive to immune checkpoint therapy.

Abstract: In certain aspects, provided herein are methods and compositions for treating or preventing cancer in a subject by conjointly administering to a subject a composition comprising a bacterium (e.g., a bacterium species or strain disclosed herein) and an immunotherapeutic agent.

Abstract: A microfluidic device is directed to sustaining a complex microbial community in direct and indirect contact with living human intestinal cells in vitro. The device includes a first microchannel having cultured cells of a human intestinal epithelium and microbiota, the first microchannel further having a first level of oxygen. The device further includes a second microchannel having cultured cells of a vascular endothelium, the second microchannel further having a second level of oxygen. The device also includes a membrane located at an interface region between the first microchannel and the second microchannel, the membrane being composed of an oxygen-permeable material or further having pores via which oxygen flows between the first microchannel and the second microchannel to form a physiologically-relevant oxygen gradient.