Previously, we have identified this subpopulation in colorectal cancer (quiescent colon cancer stem cells, QCCSCs), and find QCCSCs are sensitive to the apoptotic effect of IFN-γ, which is attributed to their high IFN-γR expression levels.
The results obtained in the current study suggested that a subpopulation of patients with MSI-L/MSS-CRC and pMMR-CRC with upregulated IFN-γ and CD8 T effector gene signatures may benefit from immunotherapy with antibodies against PD-1 and PD-L1.
These results suggest that intrinsic PD-L1 in cooperation with extrinsic IFNγ exposure in CRC may be more responsive to anti-PD-1 therapy, mainly through the CTL profile in the tumor microenvironment.
Finally, as observed in human colorectal patients, anti-PD-1 therapy had a strong response to a microsatellite-high CRC PDX that correlated with a higher number of human CD8+ IFNγ+ T cells in the tumor.
Although CRC EVs decreased HLA-DR expression in M1, M2 polarized macrophages, their effect on the secretory profile of M1 and M2 polarized macrophages was negligible.
In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer.
Fatty acid-binding protein 1 is preferentially lost in microsatellite instable colorectal carcinomas and is immune modulated via the interferon γ pathway.
HCT 116 p53<sup>+/+</sup>, HCT 116 p53<sup>-/-</sup> colorectal cancer (CRC) and OE33 esophageal adenocarcinoma (EAC) cells were treated with increasing doses of 5-FU (0.5 uM, 5 uM, 50 uM, 500 uM) or interferon gamma (IFN-γ, 10 ng/mL) in culture for 24 h and B7-H1 expression was quantified using flow cytometry and western blot analysis.
We demonstrate that stronger secretion of CXCL10 (CXCR3 ligand) and CCL5 (CCR5 ligand) and infiltration of GzmB+CD8+ cytotoxic T-lymphocytes (CTLs) and IFN-γ+CD4+ helper T-cells can be predicted by transcriptional profiling, and that CRCs with stronger T-cell immunity were proportionally skewed towards early TNM stages and lacked distant organ metastasis.
To investigate whether ATG5 deficiency could sensitize tumors to chemotherapies, we compared the antitumor effects of Interferon-gamma (IFN-γ) between Apc(Min/+)ATG5(+/+) and Apc(Min/+)ATG5(+/-) mice, as IFN-γ is a potential tumor suppressor for CRC and has been used clinically as an efficient adjuvant to chemotherapy of cancer.
A subset of colorectal cancer displayed high infiltration with activated CD8(+) cytotoxic T lymphocyte (CTL) as well as activated Th1 cells characterized by IFNγ production and the Th1 transcription factor TBET.
Thus, our results strongly support the notion that IFN-γ and IFNγR1 act as a rate-limiting factor in the development of CRC, uncovering a novel role for them in cancer biology.
Differential expression of IL-17, 22 and 23 in the progression of colorectal cancer in patients with K-ras mutation: Ras signal inhibition and crosstalk with GM-CSF and IFN-γ.
Furthermore, three of six CRC cell lines treated with IFN-γ were unable to express GBP-1 indicating that colorectal tumor cells tend to downregulate GBP-1.
Moreover, PB-NKs from CRC patients also exhibited an altered phenotype and profound defects in the ability to activate degranulation and IFN-γ production.
IL18-IL2 could significantly enhance production of IFN-γ in PBMCs in vitro and induce significant tumor regression in tumor-bearing mouse models of LLC, NCI-H460 and HCT-116 than that of IL-18 and IL-2 separately or combination using.
AdAGR2/DCs augmented the number of IFN-γ-secreting T-cells and elicited potent AGR2-specific cytotoxic T lymphocytes capable of lysing AGR2-expressing CRC cell lines.
Furthermore, combined therapy potently generated specific cytotoxic IFN-γ-secreting CD4+ T cells able to eradicate established CRC tumours after adoptive transfer.
The authors assessed polymorphisms of the interleukin: IL-1, IL-1R, IL-2, IL-4, IL-4R, IL-10, transforming growth factor (TGF)-β1, IFN-γ genes in Korean patients with colorectal cancer (n = 170) and in a normal healthy control group (n = 130) to investigate the association between theses cytokine gene polymorphisms and the risk of colorectal cancer.