Clinical and pathological significance of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer

Baş, Yılmaz; Koç, Nermin; Helvacı, Kaan; Koçak, Cem; Akdeniz, Raşit; Şahin, Havva Hande Keser

doi:10.1016/j.tranon.2020.100994

Cited by 9 publications

(14 citation statements)

References 40 publications

(33 reference statements)

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“…The presence of tumor-infiltrating lymphocytes (TIL) was quantitatively scored by counting the cells positively stained for FoxP3, CD4, CD8, CD25 and PD-1 [ 6 , 13 ]. An independent pathologist defined the area of sections to be assessed based on histology, and two independent reviewers blinded to clinicopathological data of the samples assessed the staining of each slide.…”

Section: Methodsmentioning

confidence: 99%

“…The expression of PD-L1 was quantitated using the H-score method. The sum of the intensity (0 = negative staining; 1+ = weak staining; 2+ = moderate staining; and 3+ = strong staining) and percentage of positively stained tumor cells was calculated with the H-score ranging from 0 (negative) to 300: H-score = (1 × % weakly stained cells) + (2 × % moderately stained cells) + (3 × % strongly stained cells) [ 13 ].…”

Section: Methodsmentioning

confidence: 99%

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T-Cell Infiltration and Immune Checkpoint Expression Increase in Oral Cavity Premalignant and Malignant Disorders

Surendran

Aboelkheir

et al. 2022

Biomedicines

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The immune cell niche associated with oral dysplastic lesion progression to carcinoma is poorly understood. We identified T regulatory cells (Treg), CD8+ effector T cells (Teff) and immune checkpoint molecules across oral dysplastic stages of oral potentially malignant disorders (OPMD). OPMD and oral squamous cell carcinoma (OSCC) tissue sections (N = 270) were analyzed by immunohistochemistry for Treg (CD4, CD25 and FoxP3), Teff (CD8) and immune checkpoint molecules (PD-1 and PD-L1). The Treg marker staining intensity correlated significantly (p < 0.01) with presence of higher dysplasia grade and invasive cancer. These data suggest that Treg infiltration is relatively early in dysplasia and may be associated with disease progression. The presence of CD8+ effector T cells and the immune checkpoint markers PD-1 and PD-L1 were also associated with oral cancer progression (p < 0.01). These observations indicate the induction of an adaptive immune response with similar Treg and Teff recruitment timing and, potentially, the early induction of exhaustion. FoxP3 and PD-L1 levels were closely correlated with CD8 levels (p < 0.01). These data indicate the presence of reinforcing mechanisms contributing to the immune suppressive niche in high-risk OPMD and in OSCC. The presence of an adaptive immune response and T-cell exhaustion suggest that an effective immune response may be reactivated with targeted interventions coupled with immune checkpoint inhibition.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

T-Cell Infiltration and Immune Checkpoint Expression Increase in Oral Cavity Premalignant and Malignant Disorders

Surendran

Aboelkheir

et al. 2022

Biomedicines

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“…13 Selain itu, PD-L1 juga diekspresikan pada permukaan tumor associated macrophage (TAM), myeloid derived suppressor cell (MDSC), sel dendritik , sel T dan sel B. 14 Upaya mengategorikan karsinoma ovarium berdasarkan pola TIL, ekspresi gen, dan Penilaian derajat diferensiasi karsinoma ovarium serosum berdasarkan klasifikasi WHO 2020 yaitu low grade dan high grade. Kriteria karsinoma ovarium serosum low grade jika ukuran inti bervariasi sampai <3x ukuran inti normal.…”

Section: Pendahuluanunclassified

Hubungan Ekspresi PD-L1 dengan Derajat Diferensiasi dan Densitas Til di Stroma pada Karsinoma Ovarium Serosum

Valencia¹,

Asri²,

Nizar³

2022

Heme

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Pendahuluan: Karsinoma ovarium merupakan keganasan terbanyak ke-8 pada perempuan di dunia. Karsinoma ovarium serosum merupakan keganasan ginekologi yang paling mematikan dengan perjalanan penyakit yang berbeda antara masing-masing grade. Diduga perbedaan ini disebabkan oleh adanya faktor prognostik lain yang memengaruhi luaran penyakit. Salah satu yang memengaruhi luaran penyakit adalah respon imun. Banyak efektor imun yang mendukung perkembangan tumor dan blokade efektor imun yang menimbulkan destruksi imun. Sel tumor dapat lolos dari pengenalan sel imun dan menekan aktivitas antitumor yang dimediasi sel-T sehingga mendorong pertumbuhan tumor dan metastasis melalui modulasi immune checkpoint termasuk programmed death ligand-1 (PD-L1). Tujuan penelitian: Mengetahui karakteristik dan hubungan ekspresi PD-L1 dengan derajat diferensiasi dan densitas tumor infiltrating lymphocyte (TIL) di stroma pada karsinoma ovarium serosum. Metode: Penelitian ini merupakan penelitian observasional dengan pendekatan cross sectional. Sampel penelitian ini adalah kasus karsinoma ovarium serosum dari 3 laboratorium Patologi Anatomik di kota Padang tahun 2019-2020 sebanyak 45 kasus. Derajat diferensiasi dinilai berdasarkan grading WHO 2020 dan densitas TIL dinilai berdasarkan rekomendasi The International TILs Working Group. Dilakukan pulasan imunohistokimia untuk melihat ekspresi PD-L1. Analisis bivariat menggunakan uji Chi Square dengan nilai p<0,05 dianggap bermakna. Hasil: Sebagian besar karsinoma ovarium serosum merupakan derajat diferensiasi high grade (82,2%) dan densitas TIL stroma yang tinggi (60%). Pada derajat diferensiasi high grade ekspresi PD-L1 intratumoral tinggi lebih banyak (95,7%), dibandingkan ekspresi PD-L1 rendah (68,2%). Secara statistik terdapat hubungan yang bermakna antara ekspresi PD-L1 intratumoral dengan derajat diferensiasi pada karsinoma ovarium serosum (p=0,022). Tidak terdapat hubungan antara ekspresi PD-L1 dengan densitas TIL di stroma. Kesimpulan: Semakin tinggi ekspresi PD-L1 intratumoral semakin tinggi derajat diferensiasi namun tidak terdapat hubungan antara ekspresi PD-L1 dengan densitas TIL di stroma.

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“…PD-1/PD-L1 inhibitors are currently under investigation for use in ovarian cancer in multiple clinical trials [ 8 , 13 , 14 , 15 ]. Evidence suggests that PD-1/PD-L1 blockade success in ovarian cancer differs based on histological pathology [ 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…Evidence suggests that PD-1/PD-L1 blockade success in ovarian cancer differs based on histological pathology [ 15 , 16 , 17 , 18 , 19 ]. Although these therapies show promise in some patients, responses are highly variable among ovarian tumors, and the cause of this variability is currently unknown [ 14 ]. The lack of a biomarker to predict PD-1/PD-L1 success limits patient stratification in these clinical trial patients, further lowering the efficacy rate.…”

Section: Introductionmentioning

confidence: 99%

Associations between DNA Damage and PD-L1 Expression in Ovarian Cancer, a Potential Biomarker for Clinical Response

Mann

Lee

Chen

et al. 2021

Biology

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Programmed death ligand-1 (PD-L1) inhibitors are currently under investigation as a potential treatment option for ovarian cancer. Although this therapy has shown promise, its efficacy is highly variable among patients. Evidence suggests that genomic instability influences the expression of PD-L1, but little is known about this relationship in ovarian cancer. To examine the relationship between PD-L1 expression and genomic instability, we measured DNA damage using Repair Assisted Damage Detection (RADD). We then correlated the presence of persistent DNA damage in the ovarian tumor with protein expression of PD-L1 using immunohistochemistry. Ovarian tumors showed a high prevalence of oxidative DNA damage. As the level of oxidative DNA damage increased, we saw a significant correlation with PD-L1 expression. The highest correlation between DNA damage and PD-L1 expression was observed for mucinous ovarian tumors (r = 0.82), but a strong correlation was also observed for high grade serous and endometrioid tumors (r = 0.67 and 0.69, respectively). These findings link genomic instability to PD-L1 protein expression in ovarian cancer and suggest that persistent DNA damage can be used as a potential biomarker for patient selection for immunotherapy treatment.

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Clinical and pathological significance of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression in high grade serous ovarian cancer

Cited by 9 publications

References 40 publications

T-Cell Infiltration and Immune Checkpoint Expression Increase in Oral Cavity Premalignant and Malignant Disorders

T-Cell Infiltration and Immune Checkpoint Expression Increase in Oral Cavity Premalignant and Malignant Disorders

Hubungan Ekspresi PD-L1 dengan Derajat Diferensiasi dan Densitas Til di Stroma pada Karsinoma Ovarium Serosum

Associations between DNA Damage and PD-L1 Expression in Ovarian Cancer, a Potential Biomarker for Clinical Response

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