Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer

Mo, Zhongfu; Liu, Jing; Zhang, Qiuyang; Chen, Zhiquan; Mei, Jiandong; Liu, Lunxu; Yang, Shijie; Li, Huina; Zhou, Lifei; You, Zongbing

doi:10.3892/ol.2016.4744

Cited by 76 publications

(92 citation statements)

References 32 publications

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“…22 PD-L2 has also been shown to be expressed by some solid cancers as endometrium cancer and hepatocellular cancer. 23,24 In our patients we did not find PD-L2 positive cells in the lymphocytic infiltrate and only insignificant expression on tumor cells. We therefore, excuded PD-L2 from further analysis, since its impact on tumor biology and immunosurveillance can be considered minimal.…”

Section: Discussioncontrasting

confidence: 47%

494 PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer

Chang

Ignatova

Kollmann³

et al. 2018

Journal of Investigative Dermatology

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Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study. Tissue samples of resected pulmonary metastases and available corresponding primary tumors were collected and assessed for PD-1, PD-L1 and PD-L2 expression by tumor-infiltrating lymphocytes (TILs) and tumor cells. Expression patterns were correlated with clinical outcome parameters. PD-1 and PD-L1 expression was commonly found in TILs and tumor cells. Expression levels significantly differed between metastases and primary tumors. High PD-1 expression by TILs was associated with impaired overall survival (low vs high expression (mean, 95% CI): 78 mo (60-96) vs 35 mo (25-44); p = 0.011). Additionally, the subgroup of patients, who experienced an upgrading in their TILs/PD1 status between primary and metastasis had a worse survival outcome compared with patients with the same grade or a downgrading (34 mo (26-42) vs 96 mo (72-120); p = 0.004). Thus, PD-1 expression by TILs is a strong prognostic marker in CRC patients with pulmonary spreading treated by PM. Moreover, this study provides a rationale for a therapeutic PD-1 pathway blockade in the treatment of CRC lung metastases. Future, large-scale studies are warranted to validate the findings of this single-center, retrospective analysis. Conclusions PD-1 expression by TILs is a strong prognostic marker in CRC patients with pulmonary spreading treated by PM. Moreover, this study provides a rationale for a therapeutic PD-1 pathway blockade in the treatment of CRC lung metastases. Further studies are warranted to confirm these findings in a larger study cohort

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Section: Discussioncontrasting

confidence: 47%

494 PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer

Chang

Ignatova

Kollmann³

et al. 2018

Journal of Investigative Dermatology

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“…PDCD1, often known as PD-1, is the member that has been most extensively studied and shown to negatively regulate T cell responses, in collaboration with its two ligands, PD-L1 and PD-L2 (51)(52)(53). In addition to PDCD5, other programmed cell death proteins are also known to play important roles in apoptosis and/or cell cycle progression (54)(55)(56)(57), and are also dysregulated in many types of human cancers (13,16,(58)(59)(60)(61)(62)(63). Opposite to what we observed for PDCD5, depletion of PDCD2 in human acute leukemia cells impairs their proliferation, induces cell cycle arrest and p53 activation while overexpression of PDCD2 facilitates cell growth in cancers (55,64).…”

Section: Discussionmentioning

confidence: 99%

PDCD5 regulates cell proliferation, cell cycle progression and apoptosi

Hong-xin

Wang

et al. 2017

Oncol Lett

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Abstract. Programmed cell death (PDCD)5 is cloned from human leukemia cell line TF-1. PDCD5 is one of the members of the programmed cell death protein family that is frequently involved in tumor growth and apoptosis. To investigate the molecular and cellular functions of PDCD5, the present study established a PDCD5 stably overexpressing A431 cell line and examined the role of PDCD5 in cell proliferation, cell cycle progression and apoptosis. The data demonstrated that overexpression of PDCD5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and apoptosis in A431 cells. The expression profiles of certain key regulators of these cellular events were further investigated, including P53, B cell lymphoma (BCL)-2, BCL-2 associated X protein (BAX) and caspase (CASP)3. The data demonstrated that at the transcript and protein levels, P53, BAX and CASP3 were all upregulated in the PDCD5 stably overexpressing A431 cells whereas BCL-2 was downregulated, indicating that PDCD5 acts as an important upstream regulator of P53, BCL-2, BAX and CASP3. The data suggest that PDCD5 regulates cell proliferation, cell cycle progression and apoptosis in A431 cells. PDCD5 may be a novel tumor suppressor gene, and may be potentially used for cancer treatment in the future.

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“…Particularly, we have found that 61.3% of ECs were positive for PD-1 expression and PD-L1/2 expression was increased in poorly differentiated ECs 30 . Therefore, we became interested in investigating the factors that could regulate the expression of PD-Ls in cancer cells.…”

Section: Introductionmentioning

confidence: 74%

Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines

Yang¹,

Huang²,

Mei³

et al. 2017

Int J Gynecol Cancer

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Objective Estrogen is a well-known oncogenic driver in endometrial and breast cancers. Programmed cell death protein 1 (PD-1) and its ligands PD-L1 and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in endometrial and breast cancer cell lines. Methods 17β-estradiol (E2) -induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in endometrial and breast cancer cells. Co-culture of T cells and cancer cells with E2 stimulation was performed to assess the functions of T cells. Results We found that 17β-estradiol (E2) increased expression of PD-L1, but not PD-L2 protein via activation of phosphoinositide 3-kinase (PI3K)/Akt pathway in Ishikawa and MCF-7 cells. PI3K and Akt inhibitors could block E2's effects. E2 did not increase PD-L1 mRNA transcription, but stabilized PD-L1 mRNA. E2's effects were only observed in estrogen receptor α (ERα) -positive Ishikawa and MCF-7 cells, but not in ERα-negative MDA-MB-231 cells. Co-culture of Ishikawa or MCF-7 cells with T cells inhibited expression of interferon-γ and interleukin-2 and increased Bim expression in the presence of E2. Conclusion This study provides the first evidence that estrogen up-regulates PD-L1 protein expression in ERα-positive endometrial and breast cancer cells to suppress immune functions of T cells in the tumor microenvironment, demonstrating a new mechanism of how estrogen drives cancer progression.

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Expression of PD-1, PD-L1 and PD-L2 is associated with differentiation status and histological type of endometrial cancer

Cited by 76 publications

References 32 publications

494 PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer

494 PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer

PDCD5 regulates cell proliferation, cell cycle progression and apoptosi

Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines

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