4-1BB-mediated expansion affords superior detection of in vivo primed effector memory CD8+ T cells from melanoma sentinel lymph nodes.
We have been studying the re-activation of tumor-associated antigen (TAA)-specific CD8(+) T cells in sentinel lymph nodes (SLN) of melanoma patients upon intradermal administration of the CpG-B oligodeoxynucleotide PF-3512676. To facilitate functional testing of T cells from small SLN samples, high-efficiency polyclonal T cell expansion is required. In this study, SLN cells were expanded via classic methodologies with plate- or bead-bound anti-CD3/CD28 antibodies and with the K562/CD32/4-1BBL artificial APC system (K32/4-1BBL aAPC) and analyzed for responsiveness to common recall or TAA-derived peptides. K32/4-1BBL-expanded T cell populations contained significantly more effector/memory CD8(+) T cells. Moreover, recall and melanoma antigen-specific CD8(+) T cells were more frequently detected in K32/4-1BBL-expanded samples as compared with anti-CD3/CD28-expanded samples. We conclude that K32/4-1BBL aAPC are superior to anti-CD3/CD28 antibodies for the expansion of in vivo-primed specific CD8(+) T cells and that their use facilitates the sensitive monitoring of functional anti-tumor T cell immunity in SLN.
Sluijter
B J R
BJ
Department of Surgical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
van den Hout
M F C M
MF
Stam
A G M
AG
Lougheed
S M
SM
Suhoski
M M
MM
van den Eertwegh
A J M
AJ
van den Tol
M P
MP
van Leeuwen
P A M
PA
Meijer
S
S
Scheper
R J
RJ
June
C H
CH
de Gruijl
T D
TD
Santegoets
S J A M
SJ
D053330:4-1BB Ligand / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D020014:K562 Cells; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology* / Q000601:surgery; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology*; D058950:Melanoma-Specific Antigens / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology; D017452:Receptors, IgG / Q000235:genetics; D021701:Sentinel Lymph Node Biopsy; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018984:Epitopes, T-Lymphocyte; D007378:Interleukins; D052118:Lysosomal-Associated Membrane Protein 1; D058950:Melanoma-Specific Antigens; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D017452:Receptors, IgG; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma