Identification and characterization of a tumor infiltrating CD56(+)/CD16 (-) NK cell subset with specificity for pancreatic and prostate cancer cell lines.
In a recent clinical trial, a patient exhibited regression of several pancreatic cancer metastases following the administration of the immune modulator Ipilimumab (anti-CTLA-4 antibody). We sought to characterize the immune cells responsible for this regression. Tumor infiltrating lymphocytes (TIL-2742) and an autologous tumor line (TC-2742) were expanded from a regressing metastatic lesion excised from this patient. Natural killer (NK) cells predominated in the TIL (92% CD56(+)) with few T cells (12% CD3(+)). A majority (88%) of the NK cells were CD56(bright)CD16(-). TIL-2742 secreted IFN-γ and GM-CSF following co-culture with TC-2742 and major histocompatibility complex mismatched pancreatic tumor lines. After sorting TIL-2742, the purified CD56(+)CD16(-)CD3(-) subset showed reactivity similar to TIL-2742 while the CD56(-)CD16(-)CD3(+) cells exhibited no tumor recognition. In co-culture assays, TIL-2742 and the NK subset expressed high reactivity to several pancreatic and prostate cancer cell lines and could lyse the autologous tumor as well as pancreas and prostate cancer lines. Reactivity was partially abrogated by blockade of TRAIL. We thus identified a unique subset of NK cells (CD56(bright)CD16(dim)) isolated from a regressing metastatic pancreatic cancer in a patient responding to Ipilimumab. This represents the first report of CD56(+)CD16(-) NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following the treatment with an immune modulating agent.
Frankel
Timothy L
TL
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Burns
William
W
Riley
John
J
Morgan
Richard A
RA
Davis
Jeremy L
JL
Hanada
Kenichi
K
Quezado
Martha
M
Rosenberg
Steven A
SA
Royal
Richard E
RE
D019002:CD56 Antigen / Q000032:analysis*; D045744:Cell Line, Tumor; D005260:Female; D058851:GPI-Linked Proteins; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D017452:Receptors, IgG / Q000032:analysis*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology
D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D015789:HLA-A2 Antigen; D017452:Receptors, IgG; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D007371:Interferon-gamma