Effects of anticancer agents on cell viability, proliferative activity and cytokine production of peripheral blood mononuclear cells

Abstract

We investigated the effects of anticancer agents on peripheral blood mononuclear cells for the purpose of providing data to support new translational chemoimmunotherapy regimens. Peripheral-blood mononuclear cells were treated with one of four anticancer agents (5-fluorouracil, irinotecan, cisplatin, and gemcitabine) for 2 h, after which cell viability was determined. For assessment of effects of each drug on proliferation and cytokine production, cells were stimulated with phytohemagglutinin for 48 h. As a result, the anticancer agents did not affect cell viability. Cell proliferation was unaffected by 5-fluorouracil and irinotecan but inhibited by cisplatin and gemcitabine. Treatment with gemcitabine enhanced the production of IFN-γ and decreased the number of regulatory T cells. gemcitabine treatment increased IFN-γ production among CD4 T cells but not among CD8 T cells. The results indicated that GEM had immunoregulatory properties that might support immune response against cancer. This finding has implications for designing chemoimmunotherapy strategies.

In Vivo and In Vitro Antitumor Effects of Platycodin D, a Saponin Purified from Platycodi Radix on the H520 Lung Cancer Cell

“…Marked immune deficiencies were also induced in this study after H520 cell implantation, lymphatic organ weights were noticeably reduced in tumor-bearing control mice with marked atrophic changes related to decreases of lymphoid cells in spleen and submandibular lymph nodes at histopathological observations. Although gemcitabine treatment slightly provoked the H520 cell implantation related immunosuppress in a thymic nude mice well corresponded to the previous reports [ 52 , 53 ], all three different dosages of platycodin D administrated mice showed marked and dose-dependent increase of body immune systems. Once again, the antitumor activities of platycodin D in H520 cell xenograft mice may be mediated, at least partially, by immunostimulatory effects of platycodin D in the present study.…”

“…We observed that marked decreases of stimulatory cytokines, splenic TNF- α and IL-1 β contents, and blood IFN- γ levels, and the inhibitory cytokine levels—splenic IL-10 contents were also decreased as results of decrease of T-lymphocytes after H520 cell xenograft, well corresponded previous studies [ 12 , 13 ], respectively. However, these splenic and blood cytokine decreases were effectively inhibited by treatment of platycodin D 200, 100 or 50 mg/kg, corresponded to lymphatic organ weights and histopathological inspections, but gemcitabine treatment slightly aggravated the tumor-related immunosuppress in a thymic nude mice as similar as previous reports [ 52 , 53 ].…”

The JAK/STAT pathway is involved in the upregulation of PD-L1 expression in pancreatic cancer cell lines

“…In the present study, we used 5-fluorouracil, gemcitabine and paclitaxel since they are commonly used alone or combined with other agents when treating pancreatic cancer. The concentration of each anticancer agent in our experiments was based on the plasma level of each drug when clinically used (33,34) or the concentration that was used in previous in vitro experiments (21,35,36). Consequently, the maximum concentration of 5-fluorouracil in our experiment was 10-fold higher than that used for gemcitabine and paclitaxel.…”

Macrophages as Active Nanocarriers for Targeted Early and Adjuvant Cancer Chemotherapy

“…[59a] Additionally, due to the different mechanisms of various anticancer agents, the sensitivity of macrophages to them also varies. For example, macrophages are more sensitive to cisplatin and gemcitabine than to 5‐fluorouracil and irinotecan . At last, it is also essential to ensure that the content of the loaded nanomedicines would not cause macrophage dysfunction and death before delivery to desired tumor sites.…”