| RRC ID |
68909
|
| Author |
Yorita N, Yuge R, Takigawa H, Ono A, Kuwai T, Kuraoka K, Kitadai Y, Tanaka S, Chayama K.
|
| Title |
Stromal reaction inhibitor and immune-checkpoint inhibitor combination therapy attenuates excluded-type colorectal cancer in a mouse model.
|
| Journal |
Cancer Lett
|
| Abstract |
Despite recent advances in cancer immunotherapy, the efficacy of colorectal cancer (CRC) immunotherapy regimens is limited. This study evaluated the combined effect of an anti-PD-1 antibody and a platelet-derived growth factor receptor inhibitor (imatinib) on CRC progression using an orthotopic transplanted mouse model that reproduced the three histological phenotypes of CRC (inflamed-, excluded-, and desert-type). The frequency of each of these phenotypes in 196 human CRC tissue samples was also evaluated. Excluded-type CRC had the highest frequency in human tissue samples. In the mouse model, imatinib suppressed stromal reaction and increased sensitivity to anti-PD-1 treatment in excluded-type CRC. Antitumor effect was observed in mice with excluded-type tumors only after concomitant administration of anti-PD-1 antibody and imatinib. Immunohistological analysis revealed a reduction in stromal volume and an increase in the number of CD8-positive T cells in the tumor nest following combination therapy. RNA sequencing revealed significant activation of immune-related pathways and suppression of stromal-related pathways in transplanted tumors treated with combination therapy compared with tumors treated with anti-PD-1 antibody monotherapy. This combination therapy may prove effective for CRC cases that are unresponsive to anti-PD-1 antibody monotherapy.
|
| Volume |
498
|
| Pages |
111-120
|
| Published |
2021-2-1
|
| DOI |
10.1016/j.canlet.2020.10.041
|
| PII |
S0304-3835(20)30575-9
|
| PMID |
33129954
|
| MeSH |
Aged
Animals
Antibodies / pharmacology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / metabolism
Cell Line, Tumor
Colorectal Neoplasms / drug therapy*
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / therapy*
Disease Models, Animal
Female
Humans
Imatinib Mesylate / pharmacology
Immune Checkpoint Inhibitors / pharmacology*
Immunotherapy / methods
Male
Mice
Mice, Inbred BALB C
Programmed Cell Death 1 Receptor / metabolism
Protein Kinase Inhibitors / pharmacology*
Retrospective Studies
|
| IF |
7.36
|
| Resource |
| Human and Animal Cells |
JLS-V9(RCB2651) |
