Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance

Mamat @ Yusof, Mohd Nazzary; Chew, Kah Teik; Kampan, Nirmala Chandralega; Shafiee, Mohamad Nasir

doi:10.3390/ijms242015233

Cited by 8 publications

(6 citation statements)

References 125 publications

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“…Studies indicate that ectopic endometrial tissue exhibits heightened PD-L1 expression, which may serve as a defense mechanism against immune attacks. This overexpression inhibits T cell activation within ectopic tissues, reducing their cytotoxic response and thereby decreasing the elimination of pathological tissue, allowing for its continued proliferation [ 13 , 14 , 15 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…This upregulation can inhibit the cytotoxic activity of T and B lymphocytes, reducing their effectiveness in eliminating ectopic endometrial tissue. However, the extent and precise mechanisms by which PD-1 and PD-L1 contribute to immune evasion in endometriosis remain unclear, forming the basis for further investigation in this study [ 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis

Sobstyl,

Mertowska,

Mertowski

et al. 2024

IJMS

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Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, causing pain and infertility. Despite the rather unclear etiopathogenesis, recent studies suggest the involvement of the immune system in the development and progression of endometriosis. The role of the PD-1/PD-L1 axis in the modulation of the immune response in this disease seems to be particularly interesting. This preliminary study aimed to investigate the expression of PD-1 and PD-L1 on T and B lymphocytes in peripheral blood in patients with endometriosis to assess their potential impact on disease progression. Our study involved peripheral blood samples from 80 patients diagnosed with endometriosis and 20 healthy women as a control group were analyzed. Flow cytometry was used to assess the expression of PD-1 and PD-L1 on T and B lymphocytes, and enzyme-linked immunosorbent assays were used to assess their soluble forms in serum and peritoneal fluid.in our research we observe significantly higher expression of PD-1 and PD-L1 on T and B lymphocytes was found in patients with endometriosis compared to the control group. Higher expression of both tested molecules correlated with the stage of endometriosis. The results of our preliminary studies indicate a potential role of the PD-1/PD-L1 axis in the modulation of the immune response in endometriosis. Modified expression of these proteins may contribute to immune evasion by ectopic tissues, supporting their survival and proliferation. These findings suggest that targeting PD-1/PD-L1 could be explored as a therapeutic option for the treatment of endometriosis, though further research with larger sample sizes is necessary to confirm these results and clarify the role of PD-1/PD-L1 in the pathogenesis of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis

Sobstyl,

Mertowska,

Mertowski

et al. 2024

IJMS

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“…Consequently, additional investigation is warranted to elucidate the immune microenvironment and specific immune suppression pathways in POLE-mut EC, which could potentially lead to novel therapeutic interventions for advanced-stage POLE-mutant tumors. [50][51][52] Detection and Alternative Testing Methods for Pathogenic POLE Mutations…”

Section: "Multiple-classifier" Endometrial Cancer With Diverse Charac...mentioning

confidence: 99%

The Clinical and Pathological Characteristics of POLE-Mutated Endometrial Cancer: A Comprehensive Review

Yao,

Feng,

Wang

2024

CMAR

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Endometrial cancer shows high histological and molecular heterogeneity. The POLE mutation is a significant molecular alteration in endometrial cancer, leading to the identification of a specific subtype known as POLE-mutated endometrial cancer. This subtype exhibits a high tumor mutation burden, abundant lymphocyte infiltration, and a favorable prognosis, making it a promising candidate for immune checkpoint inhibitor therapy. This paper presents a comprehensive review of the clinical and pathological characteristics, outcomes, treatment advancements, pathogenic POLE gene detection, and alternative testing methods for POLEmutated endometrial cancer.

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“…It has already been indicated that cancers with MMR deficiency, including EC, may be susceptible to programmed death 1/programmed death-ligand 1 (PD-L1) inhibitors [ 106 , 118 , 119 , 120 , 121 ]. PD-L1 expression on tumor and/or immune cells is considered a predictive factor of immunotherapy efficacy in, e.g., non-small-cell lung cancer patients [ 121 , 122 ]. It was shown that PD-L1 expression is also frequently high in EC patients [ 123 , 124 ].…”

Section: Ec Treatmentmentioning

confidence: 99%

Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection

Galant,

Krawczyk,

Monist

et al. 2024

IJMS

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Endometrial cancer (EC) accounts for 90% of uterine cancer cases. It is considered not only one of the most common gynecological malignancies but also one of the most frequent cancers among women overall. Nowadays, the differentiation of EC subtypes is based on immunohistochemistry and molecular techniques. It is considered that patients’ prognosis and the implementation of the appropriate treatment depend on the cancer subtype. Patients with pathogenic variants in POLE have the most favorable outcome, while those with abnormal p53 protein have the poorest. Therefore, in patients with POLE mutation, the de-escalation of postoperative treatment may be considered, and patients with abnormal p53 protein should be subjected to intensive adjuvant therapy. Patients with a DNA mismatch repair (dMMR) deficiency are classified in the intermediate prognosis group as EC patients without a specific molecular profile. Immunotherapy has been recognized as an effective treatment method in patients with advanced or recurrent EC with a mismatch deficiency. Thus, different adjuvant therapy approaches, including targeted therapy and immunotherapy, are being proposed depending on the EC subtype, and international guidelines, such as those published by ESMO and ESGO/ESTRO/ESP, include recommendations for performing the molecular classification of all EC cases. The decision about adjuvant therapy selection has to be based not only on clinical data and histological type and stage of cancer, but, following international recommendations, has to include EC molecular subtyping. This review describes how molecular classification could support more optimal therapeutic management in endometrial cancer patients.

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Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance

Cited by 8 publications

References 125 publications

The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis

The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis

The Clinical and Pathological Characteristics of POLE-Mutated Endometrial Cancer: A Comprehensive Review

Molecular Classification of Endometrial Cancer and Its Impact on Therapy Selection

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