Open Access
ARTICLE
Fibroblast Activation Protein-α-Positive Fibroblasts Promote Gastric Cancer Progression and Resistance to Immune Checkpoint Blockade
Xuyang Wen*, Xiaoping He†, Feng Jiao‡, Chunhui Wang§, Yang Sun‡, Xuequn Ren¶, Qianwen Li*
* Oncology Department, The 82nd Hospital of PLA, Huai’an City, Jiangsu Province, P.R. China
† IMR Residency Program of Florida Hospital, Orlando, FL, USA
‡ Department of General Surgery, The 82nd Hospital of PLA, Huai’an City, Jiangsu Province, P.R. China
§ Department of Cardiology, The 82nd hospital of PLA, Huai’an City, Jiangsu Province, P.R. China
¶ Medical Institution, Nanjing University, Nanjing, P.R. China
Oncology Research 2017, 25(4), 629-640. https://doi.org/10.3727/096504016X14768383625385
Abstract
Gastric cancer (GC) is one of the main causes of cancer death. The tumor microenvironment has a profound
effect on inducing tumor growth, metastasis, and immunosuppression. Fibroblast activation protein-a (FAP)
is a protein that is usually expressed in fibroblasts, such as cancer-associated fibroblasts, which are major
components of the tumor microenvironment. However, the role of FAP in GC progression and treatment is
still unknown. In this study, we explored these problems based on GC patient samples and experimental
models. We found that high FAP expression was an independent prognosticator of poor survival in GC
patients. FAP+
cancer-associated fibroblasts (CAFs) promoted the survival, proliferation, and migration of
GC cell lines in vitro. Moreover, they also induced drug resistance of the GC cell lines and inhibited the
antitumor functions of T cells in the GC tumor microenvironment. More importantly, we found that targeting
FAP
+
CAFs substantially enhanced the antitumor effects of immune checkpoint blockades in GC xenograft
models. This evidence highly suggested that FAP is a potential prognosticator of GC patients and a target for
synergizing with other treatments, especially immune checkpoint blockades in GC.
Keywords
Cite This Article
APA Style
Wen, X., He, X., Jiao, F., Wang, C., Sun, Y. et al. (2017). Fibroblast activation protein-α-positive fibroblasts promote gastric cancer progression and resistance to immune checkpoint blockade. Oncology Research, 25(4), 629-640. https://doi.org/10.3727/096504016X14768383625385
Vancouver Style
Wen X, He X, Jiao F, Wang C, Sun Y, Ren X, et al. Fibroblast activation protein-α-positive fibroblasts promote gastric cancer progression and resistance to immune checkpoint blockade. Oncol Res. 2017;25(4):629-640 https://doi.org/10.3727/096504016X14768383625385
IEEE Style
X. Wen et al., "Fibroblast Activation Protein-α-Positive Fibroblasts Promote Gastric Cancer Progression and Resistance to Immune Checkpoint Blockade," Oncol. Res., vol. 25, no. 4, pp. 629-640. 2017. https://doi.org/10.3727/096504016X14768383625385