title: Immune Checkpoint Blockade to Improve Tumor Infiltrating Lymphocytes for Adoptive Cell Therapy.
abstract: Tumor-infiltrating lymphocytes (TIL) has been associated with improved survival in cancer patients. Within the tumor microenvironment, regulatory cells and expression of co-inhibitory immune checkpoint molecules can lead to the inactivation of TIL. Hence, there is a need to develop strategies that disrupt these negative regulators to achieve robust anti-tumor immune responses. We evaluated the blockade of immune checkpoints and their effect on T cell infiltration and function. We examined the ability of TIL to induce tumor-specific immune responses in vitro and in vivo. TIL isolated from tumor bearing mice were tumor-specific and expressed co-inhibitory immune checkpoint molecules. Administration of monoclonal antibodies against immune checkpoints led to a significant delay in tumor growth. However, anti-PD-L1 antibody treated mice had a significant increase in T cell infiltration and IFN-γ production compared to other groups. Adoptive transfer of in vitro expanded TIL from tumors of anti-PD-L1 antibody treated mice led to a significant delay in tumor growth. Blockade of co-inhibitory immune checkpoints could be an effective strategy to improve TIL infiltration and function.
authors.affiliation: Department of Immunology, Moffitt Cancer Center, 12902 Magnolia Drive, SRB-3, Room 24314, Tampa, FL, 33612, United States of America.
authors.forename: Krithika N
authors.initials: KN
authors.lastname: Kodumudi
authors.affiliation: Department of Immunology, Moffitt Cancer Center, 12902 Magnolia Drive, SRB-3, Room 24314, Tampa, FL, 33612, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Siegel
authors.affiliation: Department of Immunology, Moffitt Cancer Center, 12902 Magnolia Drive, SRB-3, Room 24314, Tampa, FL, 33612, United States of America.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Weber
authors.affiliation: Department of Immunology, Moffitt Cancer Center, 12902 Magnolia Drive, SRB-3, Room 24314, Tampa, FL, 33612, United States of America.
authors.forename: Ellen
authors.initials: E
authors.lastname: Scott
authors.affiliation: Department of Immunology, Moffitt Cancer Center, 12902 Magnolia Drive, SRB-3, Room 24314, Tampa, FL, 33612, United States of America.
authors.forename: Amod A
authors.initials: AA
authors.lastname: Sarnaik
authors.affiliation: Department of Immunology, Moffitt Cancer Center, 12902 Magnolia Drive, SRB-3, Room 24314, Tampa, FL, 33612, United States of America.
authors.forename: Shari
authors.initials: S
authors.lastname: Pilon-Thomas
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology; D005260:Female; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse