Transcriptional and epigenetic regulation of PD-1 expression

Chi, Zengde; Lu, Yunzhe; Yang, Yinlong; Li, Bingqing; Lu, Peiyuan

doi:10.1007/s00018-020-03737-y

Cited by 15 publications

(11 citation statements)

References 70 publications

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“…Likely, gene copy number, epigenetic alterations, and microenvironment-derived stimulant regulate PD-1 expression in human cancer cells. [32][33][34][35][36] As c-Fos binds to the AP-1-binding site and activates Pdcd1 transcription in tumor-infiltrating T cells, 29 Fos reduction was retrieved among the genes regulated in NIVO-treated colon cancer cells. Also, FOXO4 and FOXO3 were regulated by NIVO treatment in human colon cancer cells, mechanism previously reported for FOXO1 in antigen-specific CD8 +T cells during chronic lymphocytic choriomeningitis virus infection.…”

Section: Discussionmentioning

confidence: 99%

“…Herein, PD-1 expression of human colon cancer cells is functional and inhibition through NIVO treatment results in a protective effect-promoting growth, reducing apoptosis and chemo/radio sensitivity in vitro and in vivo. PD-1 expression regulation has been extensively studied as DNA methylation, histone modifications, 29 glycosylation/fucosylation 30 and ubiquitination 31 were reported. While these studies mainly refer to lymphocytes, the PD-1 expression control in epithelial neoplastic cells is poorly defined.…”

Section: Discussionmentioning

confidence: 99%

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In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

Ieranò

Righelli

D’Alterio

et al. 2022

J Immunother Cancer

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BackgroundColorectal cancer (CRC) is one of the most prevalent and deadly tumors worldwide. The majority of CRC is resistant to anti-programmed cell death-1 (PD-1)-based cancer immunotherapy, with approximately 15% with high-microsatellite instability, high tumor mutation burden, and intratumoral lymphocytic infiltration. Programmed death-ligand 1 (PD-L1)/PD-1 signaling was described in solid tumor cells. In melanoma, liver, and thyroid cancer cells, intrinsic PD-1 signaling activates oncogenic functions, while in lung cancer cells, it has a tumor suppressor effect. Our work aimed to evaluate the effects of the anti-PD-1 nivolumab (NIVO) on CRC cells.MethodsIn vitro NIVO-treated human colon cancer cells (HT29, HCT116, and LoVo) were evaluated for cell growth, chemo/radiotherapeutic sensitivity, apoptosis, and spheroid growth. Total RNA-seq was assessed in 6–24 hours NIVO-treated human colon cancer cells HT29 and HCT116 as compared with NIVO-treated PES43 human melanoma cells. In vivo mice carrying HT29 xenograft were intraperitoneally treated with NIVO, OXA (oxaliplatin), and NIVO+OXA, and the tumors were characterized for growth, apoptosis, and pERK1/2/pP38. Forty-eight human primary colon cancers were evaluated for PD-1 expression through immunohistochemistry.ResultsIn PD-1+ human colon cancer cells, intrinsic PD-1 signaling significantly decreased proliferation and promoted apoptosis. On the contrary, NIVO promoted proliferation, reduced apoptosis, and protected PD-1+ cells from chemo/radiotherapy. Transcriptional profile of NIVO-treated HT29 and HCT116 human colon cancer cells revealed downregulation of BATF2, DRAM1, FXYD3, IFIT3, MT-TN, and TNFRSF11A, and upregulation of CLK1, DCAF13, DNAJC2, MTHFD1L, PRPF3, PSMD7, and SCFD1; the opposite regulation was described in NIVO-treated human melanoma PES43 cells. Differentially expressed genes (DEGs) were significantly enriched for interferon pathway, innate immune, cytokine-mediated signaling pathways. In vivo, NIVO promoted HT29 tumor growth, thus reducing OXA efficacy as revealed through significant Ki-67 increase, pERK1/2 and pP38 increase, and apoptotic cell reduction. Eleven out of 48 primary human colon cancer biopsies expressed PD-1 (22.9%). PD-1 expression is significantly associated with lower pT stage.ConclusionsIn PD-1+ human colon cancer cells, NIVO activates tumor survival pathways and could protect tumor cells from conventional therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

Ieranò

Righelli

D’Alterio

et al. 2022

J Immunother Cancer

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“…Monocytes are important components in the mononuclear phagocytic system, playing diversely essential roles during acute infection, inflammation, and tissue repair [ 16 ]. Cytokines have been widely reported to be important regulatory factors on PD-1 expression in T cells and myeloid cells through several different transcription factors and signaling pathways [ 12 , 17 ]. The results of cytokine screening to identify one(s) that affects PD-1 expression in human monocytic cell line, THP-1, we found that TGF-β and IFN-γ significantly upregulated the expression of PD-1.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of programmed cell death 1 by interferon gamma and its biological functions in human monocytes

Sri-ngern-ngam

Keawvilai

Pisitkun

et al. 2022

Biochemistry and Biophysics Reports

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“…The expression level of PD-1 in T cells is influenced by many factors. First, the transcription factors NFATc1, RBP-Jκ, STAT3, STAT4, ISGF3, FoxO1, C-FOS, and NF-κB can promote PD-1 expression, while Blimp-1 and T-bet can inhibit PD-1 expression [ 18 ]. Second, posttranscriptional modification can also affect PD-1 levels.…”

Section: Introductionmentioning

confidence: 99%

Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy

Cai

Deng

et al. 2022

Biomark Res

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Gastric cancer is characterized by high morbidity and mortality worldwide. Early-stage gastric cancer is mainly treated with surgery, while for advanced gastric cancer, the current treatment options remain insufficient. In the 2022 NCCN Guidelines for Gastric Cancer, immunotherapy is listed as a first-line option for certain conditions. Immunotherapy for gastric cancer mainly targets the PD-1 molecule and achieves therapeutic effects by activating T cells. In addition, therapeutic strategies targeting other molecules, such as CTLA4, LAG3, Tim3, TIGIT, and OX40, have also been developed to improve the treatment efficacy of gastric cancer immunotherapy. This review summarizes the molecular biomarkers of gastric cancer immunotherapy and their clinical trials.

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Transcriptional and epigenetic regulation of PD-1 expression

Cited by 15 publications

References 70 publications

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

Upregulation of programmed cell death 1 by interferon gamma and its biological functions in human monocytes

Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy

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