Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-paclitaxel Reduces the Number of Cancer-associated Fibroblasts Through Depletion of Pancreatic Stroma

作者：Miyashita, Tomoharu^*; Tajima, Hidehiro; Makino, Isamu; Okazaki, Mitsuyoshi; Yamaguchi, Takahisa; Ohbatake, Yoshinao; Nakanuma, Sinichi; Hayashi, Hironori; Takamura, Hiroyuki; Ninomiya, Itasu; Fushida, Sachio; Kishimoto, Koji; Harmon, John W.; Ohta, Tetsuo

来源：Anticancer Research, 2018, 38(1): 337-343.

DOI：10.21873/anticanres.12227

• Pancreatic cancer
• stroma
• chemoresistance
• cancer-associated fibroblast
• tumor microenvironment

Background: In this study, the effects of neoadjuvant chemotherapy (NAC) on cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma were investigated. Materials and Methods: Density of a-smooth muscle actin (alpha SMA)-positive fibroblasts in resected surgical specimens from untreated patients, patients receiving conventional gemcitabine plus S-1 (GS), and patients receiving gemcitabine plus nab-paclitaxel (GnP) was determined by hybrid cell counting. 18F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) scans and carbohydrate antigen 19-9 (CA19-9) concentrations were used to assess tumor activity before and after chemotherapy in the GnP group. Results: In this retrospective study of 65 patients, alpha SMA expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of alpha SMA-positive fibroblasts. There were significantly fewer alpha SMA-positive fibroblasts in the GnP than in the untreated and GS groups, but there was no significant difference between the latter two groups. alpha SMA density reflected a decrease in standardized uptake value on FDG-PET, but not CA19-9 concentration, after GnP chemotherapy. Conclusion: These data suggest that the GnP regimen induces stromal depletion, resulting in fewer CAFs.

• 出版日期2018-1