56P - FOXM1D in T cells promotes the transcription of PD-1 by interacting with HCFC1 and regulating the killing of renal cancer cells

Background

FOXM1D functions through interactions with proteins. We found that FOXM1D decreased in peripheral blood immune cells of renal cancer patients. It is speculated that FOXM1D is likely to regulate the expression level of immune checkpoint in immune cells through the way of interprotein interaction, and regulating the transcription of PD-1.

Methods

We detected the FD level in PBMC and CD3-positive T cells in clinical samples. PD-1 expression was detected. We performed mass spectrometry and found that HCFC1 function as a cotranscription factor. We examined the effect of FOXM1D on the HCFC1 protein. We detected the HCFC1 in cell lines with overexpression and knockdown of FOXM1D by karyoplasmic isolation. YY1 is predicted to be a transcription factor of PD-1, ChIP and Luciferase experiments to detect the binding sites to the PD-1 promoter. JKT co-culture tests with renal cancer cells in supernatant cytokine levels, observe the killer T cells. Finally, we proceed animal testing.

Results

The FD level in PBMC of renal cancer patients was significantly lower than that of normal people. The change of FOXM1D in CD3+T cells was the same as PBMC. The transcription level of PD-1 and the level of PD-1 on the surface of Jurkat-FOXM1D in cells overexpressing FOXM1D was significantly down-regulated. HCFC1 was found to function as a cotranscription factor. In immune cells, FOXM1D inhibits the entry of HCFC1 into the nucleus by interacting with the N-terminal of HCFC1, weakens the transcriptional activation of HCFC1 to YY1, and then inhibits the transcriptional regulation of PD-1 molecules. After co-culture with T cells, the cytokine in supernatant of 786O and 769P cells was changed. And the animal experiment was in progress.

Conclusions

HCFC1, as a co-transcription factor, can enhance its transcriptional function by interacting with YY1, and further regulate the transcription of immune checkpoint molecules PD-1. FOXM1D inhibits the nuclear entry of HCFC1 by interacting with the N-terminus of HCFC1, attenuates the transcriptional activation of YY1 by HCFC1, and then inhibits the transcription of various immune checkpoint molecules such as PD-1.

Legal entity responsible for the study

Fudan University Shanghai Cancer Center.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.