<p>Programmed Death-1 Receptor (PD-1) as a Potential Prognosis Biomarker for Ovarian Cancer Patients</p>

Introduction: The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest.However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to evaluate the role of programmed death-1 receptor and programmed death ligand-1 (PD-1/PD-L1) expressing lymphocytes, monocytes and granulocytes, as potential mechanism of immune escape in breast cancer patients. Also, serum levels of Bcl-2 were analyzed among patients with different stages of breast cancer. Material and Methods: The study was conducted on a total of seventy-five females; fifty-five of them represented the breast cancer females at early (24 females) and advanced (31 females) stages and 20 ages matched female donors represented the control group. Patients were recruited from the Cancer Research and Management Department, Medical Research Institute, Alexandria University. Venous blood samples obtained from all females under study were used for determination of PD-1/PD-L1 expression using flowcytometry technique and measurement of Bcl-2 serum levels using ELISA technique. Results: Significantly higher expression levels of PD-L1 were found in patients with positive lymph node, advanced tumor stage, histological grade II, tumor size T2, ER, PR, Her-2 negativity and TNBC subtype. Whilst a general increase in PD-1 positive expression between the breast cancer patients and control group regarding percentage and MFI of positive PD-1 expressing monocytes and granulocytes. Also, the results showed a highly significant association between PD-1+ and PD-L1+ expression in early and advanced breast cancer patients (p<0.0001). There was a significant increase in the mean of Bcl-2 serum concentration in patients compared to healthy individuals. Finally, the results showed that Bcl-2 serum concentration correlated positively with positive PD-L1+ expressing granulocytes. While the correlation between serum Bcl-2 and PD-1+ expressing lymphocytes, monocytes and granulocytes did not show any statistical significance. Conclusions: Our study suggested that PD-L1 could serve as an important target for antibody based immunotherapies, especially in the TNBC, where treatment options are limited. The direct correlation between PD-L1+ expression and serum Bcl-2 concentration may explore a role of apoptotic machinery in the pathogenesis of breast cancer.

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Immune checkpoint inhibitors in ovarian cancer: where do we stand?

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211039899 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110398

Author(s):

Alexandra Leary ◽

David Tan ◽

Jonathan Ledermann

Keyword(s):

Ovarian Cancer ◽

Retrospective Studies ◽

Immune Cell ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Parp Inhibitors ◽

Early Results ◽

Programmed Death ◽

Programmed Death 1 ◽

Immune Oncology

Numerous retrospective studies have demonstrated that the density of intra-tumoral immune cell infiltration is prognostic in epithelial ovarian cancer (OC). These observations together with reports of programmed death ligand-1 (PD-L1) expression in advanced OC provided the rationale for investigating the benefit of programmed death-1 (PD1) or PD-L1 inhibition in OC. Unfortunately clinical trials to date evaluating PD1/PD-L1 inhibition in patients with relapsed OC have been disappointing. In this review we will discuss early results from single agent PD1/PD-L1 inhibitors and the strategies to enhance benefit from immune-oncology agents in OC, including proposing anti-PD-L1 in combination with other agents (cytotoxics, anti-angiogenics, poly(ADP-ribose) polymerase. (PARP) inhibitors, targeted therapies or other immunotherapies), as well as evaluating these agents earlier in the disease course, or in biomarker selected patients.

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Programmed death-1 ligands and tumor infiltrating T lymphocytes in primary and lymph node metastasis of esophageal cancer patients

Diseases of the Esophagus ◽

10.1093/dote/doy063 ◽

2018 ◽

Vol 32 (3) ◽

Cited By ~ 3

Author(s):

T Konno-Kumagai ◽

F Fujishima ◽

Y Nakamura ◽

T Nakano ◽

T Nagai ◽

...

Keyword(s):

Esophageal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

T Lymphocytes ◽

Cancer Patients ◽

Node Metastasis ◽

Programmed Death ◽

Programmed Death 1

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PD-1/PDL-1 Inhibitors as Immunotherapy for Ovarian Cancer

10.1093/med/9780190248208.003.0010 ◽

2018 ◽

Author(s):

Scott Moerdler ◽

Xingxing Zang

Keyword(s):

Ovarian Cancer ◽

T Cell Activation ◽

Cell Activation ◽

Immune Escape ◽

Tumor Infiltrating Lymphocytes ◽

Immunoglobulin Superfamily ◽

Combination Therapies ◽

Programmed Death ◽

Programmed Death 1 ◽

Infiltrating Lymphocytes

Programmed death 1 (PD-1), a member of the B7-CD28 immunoglobulin superfamily, and its ligands PD-L1/PD-L2 inhibit T-cell activation. They also play a key role in the tumor microenvironment, allowing for cancer immune escape. PD-1 is induced on a variety of immune cells, including tumor-infiltrating lymphocytes (TILs), while PD-L1 is found on many types of solid tumors including ovarian cancer and some TILs. The use of immunocheckpoint inhibitors like anti-PD-1 and anti-PD-L1 therapies has been shown to reactivate the immune system to attack tumor cells. Ovarian cancers have been shown to be responsive to anti-PD-1 and anti-PD-L1 therapies, though immunocheckpoint inhibitors are not enough. Current research is evaluating combination therapies to improve response rates.

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