Analysis of PD-L1 expression in trophoblastic tissues and tumors

Lü, Bingjian; Teng, Xiaodong; Fu, Guoxiang; Bao, Lei; Tang, Jinglong; Shi, Haiyan; Lü, Weiguo; Lü, Yan

doi:10.1016/j.humpath.2018.10.001

Cited by 38 publications

(28 citation statements)

References 33 publications

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“…One important finding of the current study, similar to that reported for pure gestational trophoblastic tumors (45,46), is that all choriocarcinomatous components of mixed tumors in this series demonstrated a high level of PD-L1 expression (all tumors with at least 50% of tumor cells positive and most with over 90% expression). This observation provides a rationale for immunotherapy using checkpoint inhibitors (47).…”

Section: Discussionsupporting

confidence: 88%

Lineage-Specific Alterations in Gynecologic Neoplasms with Choriocarcinomatous Differentiation: Implications for Origin and Therapeutics

Xing

Zheng

Pallavajjala

et al. 2019

Clinical Cancer Research

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Purpose: Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well characterized. Experimental Design: To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and nongestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including five gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (two to three different components each) and six pure choriocarcinomas, for somatic mutations, single-nucleotide polymorphisms, and PD-L1 expression. Results: In mixed tumors, gynecologic-type carcinoma components demonstrated lineage-characteristic and line-age-specific alterations, with choriocarcinomatous components sharing some of these as well as demonstrating novel alterations, supporting a clonal relationship with divergent differentiation of the choriocarcinoma from the somatic carcinoma. TP53 mutation only occurred in nongestational tumors. Diffuse PD-L1 expression was characteristic of choriocarcinoma in both pure and mixed tumors but not seen in the gynecologic-type carcinoma components. Conclusions: Given that the somatic carcinomatous and choriocarcinomatous components of mixed tumors have distinct genetic alterations and biomarker expression, separate analysis of these components is required to guide targeted therapy. High PD-L1 expression suggests a role for checkpoint inhibitor-based immunotherapy in tumors with a choriocarcinoma component. The underlying mechanisms by which cancer stem cells reprogram and initiate trophoblastic retrodifferentiation in some somatic tumors warrant further investigation.

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Section: Discussionsupporting

confidence: 88%

Lineage-Specific Alterations in Gynecologic Neoplasms with Choriocarcinomatous Differentiation: Implications for Origin and Therapeutics

Xing

Zheng

Pallavajjala

et al. 2019

Clinical Cancer Research

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“…[21] Thus, the PD-1/PD-L1 axis could be involved in choriocarcinoma. Both in Lu's cohort study [22] and Cierna's translational study, [23] PD-L1 was expressed in trophoblastic tumors, especially in gestational choriocarcinoma. However, PD-L1 expression was negative (Fig.…”

Section: Discussionmentioning

confidence: 99%

Male primary mediastinal choriocarcinoma with diffuse metastases

Qiu

Wang

et al. 2019

Medicine

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Rationale: Choriocarcinoma is a rare and highly invasive gestational trophoblastic tumor that secretes high levels of human chorionic gonadotropin (hCG). As one of the uncommon non-gestational choriocarcinoma, primary mediastinal choriocarcinoma is an exceeding rare, and aggressive malignancy with poor prognosis. Patient concerns: A 26-year-old man was admitted to the hospital with cough, shortness of breath, and occasional hemoptysis. Diagnoses and intervention: Imaging examinations revealed a large mediastinal mass, diffuse nodular opacities with blurred edges in both lungs, and multiple brain lesions. Laboratory tests showed an astonishing increase of serum β-hCG. A diagnosis of primary mediastinal choriocarcinoma with advanced lung and brain metastases was finally made after 3 biopsies and immunohistochemical analyses. Surgery and radiotherapy were not applicable at the time of diagnosis, and both targeted therapy and immunotherapy were unavailable. During the first 4 cycles of trophoblastic tumor-based chemotherapy, the patient improved clinically with fewer symptoms, decreased β-hCG and reduced lesions. However, drug resistance quickly emerged, forcing an alternative chemotherapy regimen that also failed. Outcomes: The patient finally endured symptoms including headache, dizziness and vomiting, and subsequently succumbed after an overall survival time of six and half months. Lessons: Male primary choriocarcinoma is an extremely rare type of malignancy. Greater awareness, earlier diagnosis and novel treatments are urgently needed to benefit patients.

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“…Trophoblasts express several molecules that are thought to dampen alloimmune reactivity, including PD-L1, PD-L2, CD200, and FasL (15)(16)(17)(18)(19), some of which are differentially expressed throughout gestation (17). Trophoblasts are also known to produce soluble factors with an immune-modulatory action, such as soluble HLA-G (sHLA-G), transforming growth factorbeta (TGF-β), and indoleamine 2,3-dioxygenase (IDO).…”

Section: Mechanisms By Trophoblasts For Avoiding and Modulating Immunmentioning

confidence: 99%

Regulatory T Cells in Pregnancy: It Is Not All About FoxP3

et al. 2020

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In pregnancy, the semi-allogeneic fetus needs to be tolerated by the mother's immune system. Regulatory T cells (Tregs) play a prominent role in this process. Novel technologies allow for in-depth phenotyping of previously unidentified immune cell subsets, which has resulted in the appreciation of a vast heterogeneity of Treg subsets. Similar to other immunological events, there appears to be great diversity within the Treg population during pregnancy, both at the maternal-fetal interface as in the peripheral blood. Different Treg subsets have distinct phenotypes and various ways of functioning. Furthermore, the frequency of individual Treg subsets varies throughout gestation and is altered in aberrant pregnancies. This suggests that distinct Treg subsets play a role at different time points of gestation and that their role in maintaining healthy pregnancy is crucial, as reflected for instance by their reduced frequency in women with recurrent pregnancy loss. Since pregnancy is essential for the existence of mankind, multiple immune regulatory mechanisms and cell types are likely at play to assure successful pregnancy. Therefore, it is important to understand the complete microenvironment of the decidua, preferably in the context of the whole immune cell repertoire of the pregnant woman. So far, most studies have focused on a single mechanism or cell type, which often is the FoxP3 positive regulatory T cell when studying immune regulation. In this review, we instead focus on the contribution of FoxP3 negative Treg subsets to the decidual microenvironment and their possible role in pregnancy complications. Their phenotype, function, and effect in pregnancy are discussed.

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Analysis of PD-L1 expression in trophoblastic tissues and tumors

Cited by 38 publications

References 33 publications

Lineage-Specific Alterations in Gynecologic Neoplasms with Choriocarcinomatous Differentiation: Implications for Origin and Therapeutics

Lineage-Specific Alterations in Gynecologic Neoplasms with Choriocarcinomatous Differentiation: Implications for Origin and Therapeutics

Male primary mediastinal choriocarcinoma with diffuse metastases

Regulatory T Cells in Pregnancy: It Is Not All About FoxP3

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