PD-1/PD-L1 Blockade Accelerates the Progression of Atherosclerosis in Cancer Patients

Dong, Mei; Yu, Ting; Tse, Gary; Lin, Zerun; Chen, Lin; Zhang, Nan; Wang, Rujian; Liu, Tong; Zou, Lin

doi:10.1016/j.cpcardiol.2022.101527

Cited by 12 publications

(7 citation statements)

References 52 publications

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“…Immune system disorders develop because of the suppression of protective T-cell responses under pathological conditions depending on the abnormality of this PD-1 and PD-L1 pathway. Thus, the expression of PD-1 and PD-L1 has been shown in several autoimmune diseases and cancers such as atherosclerosis, periodontitis, colorectal cancer, renal cell carcinoma, and melanoma [7][8][9]. Immunotherapeutic agents targeting the PD-1/PD-L1 pathway have been developed as a novel treatment option for these diseases [10,11].…”

Section: Discussionmentioning

confidence: 99%

Does Programmed Cell Death 1 Ligand (Pd-L1) Expression Predict Recurrence in Women With Endometrioma?

Goksever Celik,

Celik,

Uhri

et al. 2024

Cureus

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The study aimed to evaluate whether there is a difference in the expression of programmed cell death 1 ligand (PD-L1) in the cell lining of endometrioma between cases with and without recurrent disease. Additionally, we sought to assess the effect of cyst size and serum CA125 level on the expression of PD-L1 staining. The pathological specimens were immunohistochemically stained for PD-L1 in women who underwent surgery for endometrioma. All patients were evaluated to confirm if their endometriomas had recurred or not. A total of 36 patients who underwent surgery for endometrioma were included. The study population was divided into two groups according to their recurrence status. The study group (having recurrence) (n=12) and the control group (having no recurrence) (n=24) were compared regarding their demographic and clinical characteristics and PD-L1 staining. PD-L1 staining and the intensity of PD-L1 staining did not differ between the patients with and without recurrence. No variable, including parity, cyst size, serum CA125 level, and PD-L1 staining, was found to be significant in determining recurrence. No significant difference was found between the groups with and without PD-L1 staining in terms of cyst size and serum CA125 level. Although we have shown that PD-L1 expression could not be used for the prediction of recurrence, further studies are needed to assess this issue and to guide the development of new immunotherapeutic agents on this basis.

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Section: Discussionmentioning

confidence: 99%

Does Programmed Cell Death 1 Ligand (Pd-L1) Expression Predict Recurrence in Women With Endometrioma?

Goksever Celik,

Celik,

Uhri

et al. 2024

Cureus

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“…Anticancer drugs have side effect profiles such as increased toxicity to the cardiovascular system [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. For doxorubicin‐related cardiotoxicity, interventions that reduce oxidation stress have failed to reduce cardiac damage in patients [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin‐induced myocardial injury

Zhang

Xie

et al. 2023

Cancer Innovation

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BackgroundDoxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose‐dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin‐induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin‐induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro.MethodsAdult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate‐buffered saline, doxorubicin, and doxorubicin with resveratrol).ResultsCompared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α‐smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels.ConclusionDoxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin‐induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

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“…Interestingly, hypercholesterolemia increased PD-L1 expression on myeloid cells and increased PD-1 expression on T-cells, suggesting a possible compensatory response in which PD-L1-PD-1 interaction restrains the inflammatory response during atherosclerosis progression ( 135 , 136 ). In this context, cancer patients who receive blocking antibodies targeting PD-L1 or PD-1 have an aggravation of atherosclerotic cardiovascular disease ( 137 ).…”

Section: The Role Of Cell-cell Contacts Between Efferocytes and T-cellsmentioning

confidence: 99%

Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis

Ngai,

Sukka,

Tabas

2024

Front. Immunol.

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The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can contribute to the development of chronic inflammatory diseases. Important among these diseases is atherosclerosis, which refers to focal lesions in the arterial intima driven by elevated apolipoprotein B-containing lipoproteins, notably low-density lipoprotein (LDL), and characterized by the formation of a plaque composed of inflammatory immune cells, a collection of dead cells and lipids called the necrotic core, and a fibrous cap. As the disease progresses, the necrotic core expands, and the fibrous cap becomes thin, which increases the risk of plaque rupture or erosion. Plaque rupture leads to a rapid thrombotic response that can give rise to heart attack, stroke, or sudden death. With marked lowering of circulating LDL, however, plaques become more stable and cardiac risk is lowered—a process known as atherosclerosis regression. A critical aspect of both atherosclerosis progression and regression is the crosstalk between innate (myeloid cells) and adaptive (T-lymphocytes) immune cells. Myeloid cells are specialized at clearing apoptotic cells by a process called efferocytosis, which is necessary for inflammation resolution. In advanced disease, efferocytosis is impaired, leading to secondary necrosis of apoptotic cells, inflammation, and, most importantly, defective tissue resolution. In regression, efferocytosis is reawakened aiding in inflammation resolution and plaque stabilization. Here, we will explore how efferocytosing myeloid cells could affect T-cell function and vice versa through antigen presentation, secreted factors, and cell-cell contacts and how this cellular crosstalk may contribute to the progression or regression of atherosclerosis.

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PD-1/PD-L1 Blockade Accelerates the Progression of Atherosclerosis in Cancer Patients

Cited by 12 publications

References 52 publications

Does Programmed Cell Death 1 Ligand (Pd-L1) Expression Predict Recurrence in Women With Endometrioma?

Does Programmed Cell Death 1 Ligand (Pd-L1) Expression Predict Recurrence in Women With Endometrioma?

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin‐induced myocardial injury

Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis

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