Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer

Chatterjee, Jayanta; Dai, Wei; Aziz, Nor Haslinda Abd; Teo, Pei Yun; Wahba, John; Phelps, David L.; Maine, Christian J.; Whilding, Lynsey M.; Dina, Roberto; Trevisan, Giorgia; Flower, Kirsty; George, Andrew J.T.; Ghaem‐Maghami, Sadaf

doi:10.1158/1078-0432.ccr-16-2366

Cited by 50 publications

(55 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ovarian cancer, it has been shown that total PD-L1 and CD14þ/PD-L1þ expression in the peripheral blood can accurately differentiate between benign tumours and Stage I malignant ovarian tumours as well as showing significant differential expression between early and late-stage disease [68].…”

Section: Blood Basedmentioning

confidence: 99%

The role of biomarkers in endometrial cancer and hyperplasia: a literature review

et al. 2019

Self Cite

View full text Add to dashboard Cite

Introduction: Endometrial cancer is the most common gynaecological cancer and its incidence is rising due to increasing obesity rates. We are also seeing an increasing trend of young women diagnosed with either endometrial cancer or its precancerous state, endometrial hyperplasia. Diagnosis is dependent on invasive testing and there is no screening tool available for either general or high-risk population groups.Whilst vast amounts of research have been undertaken in higher-profile cancers such as ovarian and cervical, endometrial cancer is comparatively less investigated. Aim: In this literature review, we summarise the existing literature in understanding the role of tumour biomarkers for endometrial cancer and its preceding condition of endometrial hyperplasia. Method: NICE Healthcare Databases Search tool was used to search Embase, Medline and PubMed databases for relevant articles. Conclusion: There is currently no routinely used biomarker in endometrial cancer for diagnostic or prognostic purposes. Given the establishment of new genomic classifications of endometrial cancers, the use of biomarkers to drive therapeutic approaches will be the cornerstone for individualised cancer care in the coming decades. ARTICLE HISTORY

show abstract

Section: Blood Basedmentioning

confidence: 99%

The role of biomarkers in endometrial cancer and hyperplasia: a literature review

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…These observations suggest that PD-L1 expression may reflect aggressive biological potential and play an important role in tumour immune escape. For example, in ovarian cancer, the differential expression of immunological markers related to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers [13]. PD-L1 is also expressed by macrophages in ovarian cancer and is strongly associated with both effector and regulatory tumour infiltrating lymphocyte (TIL) subsets [14].…”

Section: Introductionmentioning

confidence: 99%

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

Xie

Huang

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. Methods: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. Results: Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-γ, TNF-α, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8⁺ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1⁺CD8⁺T cells. Conclusion: We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.

show abstract

“…TICS is built on the principles of an allogeneic response but has been specifically optimised to quantify activation of multiple human lymphocyte subsets and subsequent cancer cell killing upon PD-1/L1 blockade. Although we have previously reported the differential expression pattern and prognostic value of PD-L1 on human myeloid cells isolated from ovarian cancer patients [16], removal of monocytes from TICS is necessary to demonstrate the effects of immune checkpoint blocking antibody and to reduce donor-to-donor variability.…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade

Natoli

Bonito

Robinson

et al. 2020

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

Immune checkpoint blocking antibodies are currently being tested in ovarian cancer (OC) patients and have shown some responses in early clinical trials. However, it remains unclear how human OC cancer cells regulate lymphocyte activation in response to therapy. In this study, we have established and optimised an in vitro tumour-immune co-culture system (TICS), which is specifically designed to quantify the activation of multiple primary human lymphocyte subsets and human cancer cell killing in response to PD-1/L1 blockade. Human OC cell lines and treatment naïve patient ascites show differential effects on lymphocyte activation and respond differently to PD-1 blocking antibody nivolumab in TICS. Using paired OC cell lines established prior to and after chemotherapy relapse, our data reveal that the resistant cells express low levels of HLA and respond poorly to nivolumab, relative to the treatment naïve cells. In accordance, knockdown of IFNγ receptor expression compromises response to nivolumab in the treatment naïve OC cell line, while enhanced HLA expression induced by a DNA methyltransferase inhibitor promotes lymphocyte activation in TICS. Altogether, our results suggest a 'cross resistance' model, where the acquired chemotherapy resistance in cancer cells may confer resistance to immune checkpoint blockade therapy through down-regulation of antigen presentation machinery. As such, agents that can restore HLA expression may be a suitable combination partner for immunotherapy in chemotherapy-relapsed human ovarian cancer patients.Keywords Human ovarian cancer · PD-1/PD-L1 blockade · Immune resistance · Human cancer/immune co-culture AbbreviationsDNMTi DNA methyltransferase inhibitor GFP Green fluorescent protein MSI Microsatellite instability OC Ovarian cancer PBMCs Peripheral blood mononuclear cells PD-1 Programmed cell death protein 1 PD-L1Programmed death-ligand 1 TICS Tumour-immune co-culture system TMB Tumour mutational burden * Sadaf Ghaem-Maghami

show abstract

Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer

Cited by 50 publications

References 25 publications

The role of biomarkers in endometrial cancer and hyperplasia: a literature review

The role of biomarkers in endometrial cancer and hyperplasia: a literature review

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade

Contact Info

Product

Resources

About