Background
Pancreatic cancer (PC) is one of the malignancies with the worst prognosis because of rapid metastasis as well as invasion to surrounding tissues even with chemotherapy. Cellular immunotherapy is a candidate to improve the difficulty of treatment for PC. We retrospectively studied the overall survival (OS) of PC patients treated with a combination of chemotherapy and NK cell-enriched immunotherapy (NK-CT) and the relationship between OS and immunological changes in peripheral blood lymphocytes (PBL) before and after the immunotherapy.
Patients and Methods
We studied 77 patients with advanced PC received NK-CT in our clinic since 2004. In this study, out of all PC patients, 46 patients with ECOG Performance Status 0-1 were retrospectively analyzed to determine the clinical outcome and the immunological changes of PBL after NK-CT. Median age was 65 years, and 74% of them had distant metastases. Almost all cases received chemotherapy with gemcitabine and/or S-1. NK-CT was carried out average 10 times every two weeks with chemotherapy in parallel. NK cells were expanded by a culture method using CD52-costimulation of peripheral blood mononuclear cells (PBMC) isolated from cancer patients (Cytotherapy 18:80, 2016). Muromonab and alemtuzumab were used for costimulation of PBMC. Immunological changes of PBL were assessed using flow cytometry.
Results
The estimated OS was 15.5 months and the 1-year survival rate was 63%, and the median survival time after NK-CT was 11.0 months. NK-CT was well tolerated by all patients without treatment-related toxicities excluding transient fever (~38oC). We investigated the effect of infused NK cells on clinical outcome and the relationship between immunological changes of PBL and survival time after NK-CT. The result suggests that the proportion and number of infused NK cells do not correlate to the length of survival. However, when 46 patients were divided into the short-term survivors (<11 months, median 6.1 months, n = 19) and the long-term survivors (≧11 months, median 17.4 months, n = 27) after NK-CT, we found a significant increase in NK cell cytotoxic activity and the numbers of lymphocytes, NK cells, NKG2D+ cells, and a significant decrease in the ratios of CD4/CD8 T cells in PBL in the long-term survivors, while there were no significant changes in any indicators in the short-term survivors.
Conclusions
The findings suggest that sustained enhancement of cytotoxic profiles in circulating lymphocytes after NK-CT may contribute to survival extension observed in this study.