Analysis of TCGA dataset revealed that the mRNA expression levels of PD-L1 and PD-L2, the IFN-γ gene signature and the CD8 T effector gene signature were significantly upregulated in MSI-H tumors compared with MSI-L/MSS tumors.
Bone marrow MDSC were induced to differentiate in vitro into tumor MDSC-like cells by treating with IFN-γ, IL-13, and GM-CSF for 48 h. This treatment significantly elevated Arg1 and Nos2 levels, activated the T cell-suppressive function of MDSC, increased VDR expression 50-fold, and made the MDSC responsive to 1,25(OH)<sub>2</sub>D treatment.
This was associated with enhanced T-cell exhaustion, and severely attenuated T-cell antitumor effector responses including reduced expression of IFN-γ and perforin at the tumor site.
During pregnancy, CD56<sup>dim</sup> and CD56<sup>bright</sup> NK cells displayed enhanced functional responses to both infected and tumor cells, with increased expression of degranulation markers and elevated frequency of NK cells producing IFN-γ.
Under this circumstance, the PD-1 molecule on the human T lymphocyte surface is in contact with the PD-L1 molecule on the human tumor cells and, thus, the formatin of the PD-L1/PD-1 pathway in the tumor microenvironment.Treatment with anti-PD-1 monoclonal antibody (mAb) significantly inhibited the growth of both CDX and PDX tumors, but not non-human NCG models (without allogeneic human PBMCs and IFN-γ) .
The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of CD4<sup>+</sup>/CD8<sup>+</sup> and the secretion of interleukin (IL)-2 and interferon-γ, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulating <i>Bax</i> and <i>Caspase-3</i> and down-regulating <i>Bcl-2</i>.
The therapeutic reconstruction released IFNγ at the LRR site and eliminated cancer cells, significantly decreased tumor burden (P<0.05), and increased survival by 33% (P<0.05) compared to sham reconstruction.
Unlike CFZ-CD, the locally injected CFZ-pTA-alb protected or enhanced CD8<sup>+</sup> T cell population in tumors, helped develop splenocytes with tumor-specific interferon-γ response, and delayed tumor development on the contralateral side in immunocompetent mice (but not in athymic nude mice), supporting that CFZ-pTA-alb contributed to activating antitumor immunity.
The importance of IFN-γ in upregulating the PD-L1 expression in various tumors, and the effects of other essential cytokines in the tumor microenvironment (TME), need to be further elucidated.
Mechanistically, IFNγ derived from immunotherapy-activated CD8<sup>+</sup> T cells and radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate-cystine antiporter xc<sup>-</sup>, resulting in reduced cystine uptake, enhanced tumor lipid oxidation and ferroptosis, and improved tumor control.
GLPG1690 decreased irradiation-induced C-C motif chemokine ligand-11 in tumors and levels of interleukin-9, interleukin-12p40, macrophage colony-stimulating factor and interferon γ in adipose tissue adjacent to the tumor.
More importantly, in a Huh-7 xenograft mouse model, GPC3CAR-T cells significantly reduced the tumour burden companied with the secretion of high levels of IFN-γ.
Followingstimulation, expressions of CD107a and intracellular IFN-γ were elevated in tumor CMV positive patients while the TNF-α secretion was decreased.
Combining CAI with 1-MT or DMF disrupted PD-1 expression and promoted IFN-γ production in CD8<sup>+</sup> T cells, and it also increased T lymphocyte infiltration in the tumor microenvironment, inhibited tumor growth and prolonged the life spans of tumor-bearing mice.
We demonstrated that Astragaloside III significantly elevated the expression of natural killer group 2D (NKG2D), Fas, and interferon-γ (IFN-γ) production in NK cells, leading to increased tumor-killing ability.
After cessation of palbociclib treatment genes associated with differentiation, for example, <i>P63</i>, inflammation, IFNγ response, and antigen processing and presentation remained suppressed in the tumor and surrounding stroma.
We showed that AT EC exposed in vitro to TGF-β (tumor growth factor-β), TNF-α (tumor necrosis factor-α), and IFN-γ (interferon-γ) undergo EndoMT with progressive loss of endothelial markers.
In addition, IL-37 indirectly up-regulated the expression of major histocompatibility class II molecules, CD86 and CD40 on DCs by acting on tumor cells; IL-37 also indirectly enhanced the anti-tumor effect of T lymphocytes by stimulating DCs to secrete cytokines such as IL-2, IL-12, IL-12p70, interferon-α (IFN-α) and IFN-γ.
Tumor resistance was observed in the context of T-cell programmed death-1 expression and defects in interferon gamma and antigen presentation pathway components.
We show that while inhibiting tumor IFNG signaling decreases interferon-stimulated genes (ISGs) in cancer cells, it increases ISGs in immune cells by enhancing IFNG produced by exhausted T cells (T<sub>EX</sub>).
Depletion of NK cells in α-GalCer-treated mice showed a lower frequency of IFN-γ-producing CD4<sup>+</sup> and CD8<sup>+</sup> T cells in the tumor and prevented the α-GalCer-induced tumor growth.
Pretreatment of mice with large established tumors using the STAT1-activating cytokine interferon-γ (IFNγ), the TLR3 ligand poly(I:C), and an anti-IL-10 antibody sensitized tumors to ICB by attracting IFNγ-producing NK cells into the tumor, resulting in increased cure rates.