2. Academic Validation
  3. KrasG12D mutation contributes to regulatory T cell conversion through activation of the MEK/ERK pathway in pancreatic cancer

KrasG12D mutation contributes to regulatory T cell conversion through activation of the MEK/ERK pathway in pancreatic cancer

  • Cancer Lett. 2019 Apr 1;446:103-111. doi: 10.1016/j.canlet.2019.01.013.
He Cheng 1,  Kun Fan 1,  Guopei Luo 1,  Zhiyao Fan 1,  Chao Yang 1,  Qiuyi Huang 1,  Kaizhou Jin 1,  Jin Xu 1,  Xianjun Yu 2,  Chen Liu 3
Affiliations

Affiliations

  • 1 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China.
  • 2 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China. Electronic address: yuxianjun@fudanpci.org.
  • 3 Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Shanghai Pancreatic Cancer Institute, Shanghai, China. Electronic address: liuchen@fudanpci.org.
PMID: 30664964 DOI: 10.1016/j.canlet.2019.01.013
Abstract

Genetic alterations have been attributed to the abnormal immune microenvironment in Cancer. However, the relationship between the KrasG12D mutation and regulatory T cells (Tregs) in pancreatic Cancer remains unclear. In this study, we found that KrasG12D mutation status as determined by ddPCR correlated with high levels of Treg infiltration in resectable pancreatic Cancer tissues. Compared to wild-type tumour cells, tumours cells with the KrasG12D mutation were associated with higher levels of Tregs, and knockout of the KrasG12D mutation reversed this effect. In addition, overexpression of the KrasG12D mutation in wild-type Kras tumour cells resulted in conversion of CD4+CD25- T cells into Tregs. We also found that in tumour cells, the KrasG12D mutation activated the MEK/ERK pathway, thereby up-regulating the levels of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), which induced Treg conversion. In summary, KrasG12D mutation plays a critical role in Treg conversion and contributes to an immunosuppressive tumour microenvironment in pancreatic Cancer. These results provide new insights into the relationship between gene mutation and immune escape.

Keywords

IL-10; Immunosuppressive; Kras(G12D) mutation; Pancreatic cancer; TGF-β.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z