|
Status |
Public on Jun 30, 2021 |
Title |
Immune modulation underpins the anti-cancer activity of HDAC inhibitors |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
We have explored at the genome-wide expression level the effects of the novel HDAC inhibitor CXD101. In human CRC cell lines, a diverse set of differentially expressed genes were up- and down-regulated. Functional profiling of the expression data highlighted immune-relevant concepts related to antigen processing and natural killer (NK) cell mediated cytotoxicity. Similar gene profiles were apparent when global gene expression was investigated in murine CT26 cells treated with CXD101, which were also apparent in syngeneic CT26 tumours growing in vivo. The ability of CXD101 to affect immune-relevant gene expression coincided with changes in the tumour micro-environment (TME), especially in the sub-groups of tumour-infiltrating lymphocytes which occurred upon CXD101 treatment. The altered TME reflected synergistic anti-tumour activity apparent when CXD101 was combined with immune oncology (IO) agents, like anti-PD1 and anti-CTLA4.The ability of CXD101 to instate antigen presentation and augment NK activity in the TME, combined with the synergy between HDAC inhibitors and IO agents, provides a powerful rationale for exploring the combination effect in human cancers.
|
|
|
Overall design |
Examination of expresion profile of human and murine colorectal cancer cells treated with HDAC inhibitor
|
|
|
Contributor(s) |
Blaszczak W, Zhu H, Liu G, Zheng S, Barczak W, Kanapin A, Samsonova A, La Thangue NB |
Citation(s) |
33773029 |
|
Submission date |
Sep 17, 2020 |
Last update date |
Sep 29, 2021 |
Contact name |
Alexander Kanapin |
E-mail(s) |
[email protected]
|
Phone |
+78123636939
|
Organization name |
St Petersburg Universoty
|
Department |
Institute for Translational Biomedicine
|
Street address |
7/9 University Emb.
|
City |
St. Petersburg |
ZIP/Postal code |
199034 |
Country |
Russia |
|
|
Platforms (2) |
|
Samples (18)
|
GSM4794595 |
SW620 CDX101 cell line RNA-seq replicate 1 |
GSM4794596 |
SW620 CXD101 cell line RNA-seq replicate 2 |
GSM4794597 |
CT26 cell line RNA-seq replicate 1 |
GSM4794598 |
CT26 cell line RNA-seq replicate 2 |
GSM4794599 |
CT26 cell line RNA-seq replicate 3 |
GSM4794600 |
CT26 CDX101 cell line RNA-seq replicate 1 |
GSM4794601 |
CT26 CXD101 cell line RNA-seq replicate 2 |
GSM4794602 |
CT26 CXD101 cell line RNA-seq replicate 3 |
GSM4794603 |
Colon26 cells from syngeneic mouse model replicate 1 |
GSM4794604 |
Colon26 cells from syngeneic mouse model replicate 2 |
GSM4794605 |
Colon26 cells from syngeneic mouse model replicate 3 |
GSM4794606 |
Colon26 cells from syngeneic mouse model CXD101 treatment replicate 1 |
GSM4794607 |
Colon26 cells from syngeneic mouse model CXD101 treatment replicate 2 |
GSM4794608 |
Colon26 cells from syngeneic mouse model CXD101 treatment replicate 3 |
GSM4794609 |
Colon26 cells from syngeneic mouse model CXD101 treatment replicate 4 |
|
Relations |
BioProject |
PRJNA664188 |
SRA |
SRP283100 |