| RRC ID |
71905
|
| Author |
Kabashima A, Matsuo Y, Ito S, Akiyama Y, Ishii T, Shimada S, Masamune A, Tanabe M, Tanaka S.
|
| Title |
cGAS-STING signaling encourages immune cell overcoming of fibroblast barricades in pancreatic cancer.
|
| Journal |
Sci Rep
|
| Abstract |
Immune checkpoint blockade (ICB) treatment improves the prognosis of several types of solid tumors, however, responsiveness to ICB therapy remains low in pancreatic ductal adenocarcinoma (PDACs), which has a rich tumor microenvironment (TME). The TME is composed of various stromal cells, including cancer-associated fibroblasts (CAFs), which contribute to the establishment of an immunosuppressive microenvironment. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an innate immune pathway that results in the upregulation of immune cell recruiting-cytokines and anti-tumor efficacy. In this study, we aimed to investigate the impact of cGAS-STING expression and the presence of CAFs upon immune cell infiltration in PDACs. cGAS and STING co-expressing PDAC cases showed favorable survival, with many cytotoxic CD8 + T cell infiltrations from the stromal component adjacent to the cancer cells toward cancer cells, but not in cGAS-STING signaling defected PDAC cases. The signatures of tumor-restrain CAFs were expressed in tumors with cGAS-STING signaling. Finally, transwell co-culture experiments demonstrated that immune cell infiltration was impeded by the presence of CAFs, but not by activation of cGAS-STING signaling. In conclusion, pro-infiltration signals, such as cGAS-STING, and characterization of CAFs are crucial in defeating CAF barricades and encouraging immune cell infiltration in PDACs.
|
| Volume |
12(1)
|
| Pages |
10466
|
| Published |
2022-6-30
|
| DOI |
10.1038/s41598-022-14297-5
|
| PII |
10.1038/s41598-022-14297-5
|
| PMID |
35773436
|
| PMC |
PMC9247053
|
| MeSH |
Cancer-Associated Fibroblasts* / metabolism
Cancer-Associated Fibroblasts* / pathology
Carcinoma, Pancreatic Ductal* / metabolism
Carcinoma, Pancreatic Ductal* / pathology
Humans
Membrane Proteins* / metabolism
Nucleotidyltransferases* / metabolism
Pancreatic Neoplasms* / metabolism
Pancreatic Neoplasms* / pathology
Signal Transduction
Tumor Microenvironment
|
| IF |
3.998
|
| Resource |
| Human and Animal Cells |
KLM-1(RCB2138)
hPSC-1(RCB3586) |
