title: Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice.
abstract: Adoptive cell transfer (ACT) melanoma immunotherapy typically employs acutely activated effector CD8+ T cells for their ability to rapidly recognize and clear antigen. We have previously observed that effector CD8+ T cells are highly susceptible to melanoma-induced suppression, whereas memory CD8+ T cells are not. Although memory T cells have been presumed to be potentially advantageous for ACT, the kinetics of local and systemic T cell responses after effector and memory ACT have not been compared. B16F10 melanoma cells stably transfected to express very low levels of the lymphocytic choriomeningitis virus (LCMV) peptide GP33 (B16GP33) were inoculated into syngeneic C57BL/6 mice. Equal numbers of bona fide naïve, effector, or memory phenotype GP33-specific CD8+ T cells were adoptively transferred into mice 1 day after B16GP33 inoculation. The efficacy of ACT immunotherapy was kinetically assessed using serial tumor measurements and flow cytometric analyses of local and systemic CD8+ T cell responses. Control of B16GP33 tumor growth, persistence of adoptively transferred CD8+ cells, intratumoral infiltration of CD8+ T cells, and systemic CD8+ T cell responsiveness to GP33 were strongest after ACT of memory CD8+ T cells. Following surgical tumor resection and melanoma tumor challenge, only mice receiving memory T cell-based ACT immunotherapy exhibited durable tumor-specific immunity. These findings demonstrate how the use of non-expanded memory CD8+ T cells may enhance ACT immunotherapeutic efficacy.
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI, 53792-7375, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Contreras
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI, 53792-7375, USA.|Surgical Service, William S. Middleton Memorial VA Hospital, Madison, WI, USA.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Sen
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI, 53792-7375, USA.|Surgical Service, William S. Middleton Memorial VA Hospital, Madison, WI, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tatar
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI, 53792-7375, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Mahvi
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI, 53792-7375, USA.
authors.forename: Justin V
authors.initials: JV
authors.lastname: Meyers
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI, 53792-7375, USA.
authors.forename: Prakrithi
authors.initials: P
authors.lastname: Srinand
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, WI, USA.
authors.forename: Marulasiddappa
authors.initials: M
authors.lastname: Suresh
authors.affiliation: Section of Surgical Oncology, University of Wisconsin School of Medicine and Public Health, J4/703 Clinical Sciences Center, 600 Highland Avenue, Madison, WI, 53792-7375, USA. cho@surgery.wisc.edu.|Surgical Service, William S. Middleton Memorial VA Hospital, Madison, WI, USA. cho@surgery.wisc.edu.
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D006023:Glycoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C094244:glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
keywords: Adoptive transfer; Effector; Immunotherapy; Melanoma; Memory; T cell