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.