Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer

Bae, Sang Byung; Cho, Hyun Deuk; Oh, Mee‐Hye; Lee, Ji Hye; Jang, Si Hyong; Hong, Soon Auck; Cho, Junhun; Kim, Sung Yong; Han, Sun Wook; Lee, Jong Eun; Kim, Hee Jin; Lee, Hyun Ju

doi:10.4048/jbc.2016.19.3.242

Cited by 72 publications

(72 citation statements)

References 30 publications

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“…No statistically significant associations were found between PDL1TC and other clinicopathologic parameters. These findings are consistent with most studies found in the literature (43)(44)(45)(46). The association between PDL1TC and HER2 status remains controversial, though (41,47).…”

Section: Figure 1 (A) Pd-l1 Expression In Tumor Cells (×20) (B) Pd-supporting

confidence: 92%

PD-L1 Expression and Tumor-infiltrating Lymphocytes in Breast Cancer: Clinicopathological Analysis in Women Younger than 40 Years Old

Evangelou

Papoudou‐Bai

Karpathiou

et al. 2020

In Vivo

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Background/Aim: To evaluate the association between programmed cell death ligand 1 (PD-L1) expression on both tumor cells (TC) and inflammatory cells (IC), tumor infiltrating lymphocytes (TILs), CD3 + and CD8 + lymphocytes and other clinicopathological parameters in primary infiltrative breast cancer (IBC) of young women, a population shown to have a worse prognosis. Materials andMethods: A retrospective study was performed collecting data from patients younger than 40 years old. Forty-five young women with IBC were included. Whole tissue sections were used to evaluate all parameters. Results: Twenty percent (20%) of cases showed PD-L1 expression by tumor cells (PDL1TC) and 44.4% showed PD-L1 expression by immune cells (PDL1IC). Furthermore, 28.88% revealed high stromal TILs. PDL1TC and PDL1IC expression were significantly associated with tumor diameter and expression of estrogen (ER) and progesterone (PR) receptors and Ki67. PDL1TC expression was also associated with grade. High TILs were associated with tumor diameter, ER and Ki67 expression. PDL1TC, PDL1IC expression and TILs were associated with the density of CD3 + and CD8 + lymphocytes. Conclusion: Our results are similar to those of other age groups, as reported in the literature.

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Section: Figure 1 (A) Pd-l1 Expression In Tumor Cells (×20) (B) Pd-supporting

confidence: 92%

PD-L1 Expression and Tumor-infiltrating Lymphocytes in Breast Cancer: Clinicopathological Analysis in Women Younger than 40 Years Old

Evangelou

Papoudou‐Bai

Karpathiou

et al. 2020

In Vivo

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“…Recently, the combination of PD‐L1 and tumor‐infiltrating lymphocytes (TILs) has been investigated in TNBC, and the reported findings confirm the importance of examining both PD‐L1 and TILs for clinical outcome prediction . In the current study, we evaluated PD‐L1 and a set of other relevant immune markers in relation to their association with clinical outcome in a series of HER2‐positive cases.…”

Section: Introductionmentioning

confidence: 69%

“…There have been conflicting results in the literature as to whether PD‐L1 expression is a favorable or adverse prognostic factor for breast cancer patients managed with standard therapy. Most of the published studies have dealt with patients with diverse subtypes of breast cancer, with the exception of several studies which focused on TNBC exclusively . The discordance of reported results may relate to differences in methods of assessment, numeric thresholds, antibody clones or composition of cohorts.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer

et al. 2018

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Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. However, to date, the combination of PD1/PD-L1 expression and tumor-infiltrating lymphocytes (TILs) and antigen-presenting cells has been only minimally reported in breast carcinoma, in particular in relation to HER2-positive cases. The goal of this study was to evaluate both cellular tumoral immune reaction and PD-L1/PD1 distribution in HER2-positive cases, as well as any associations with clinical outcome using conventional chemotherapy combined with HER2 blocking. Multicolor immunohistochemical multiplex assays simultaneously demonstrating PD1, PD-L1, and CD8 or PD-L1, CD3, and CD163 were performed on tissue microarrays (TMA) representing 216 pretreatment cases of HER2-positive invasive breast carcinoma. PD-L1 expression was identified in 38 cases (18%), including 12 cases (6%) with PD-L1 labeling of tumor cells and 26 cases (12%) with PD-L1 labeling of immune cells only. Ten of 12 cases with PD-L1 staining of tumor cells showed staining of associated immune cells as well. With this assay method, PD1 was detectable in many fewer cases (6 cases or 3%). PD-L1 expression was positively associated with high Nottingham grade, negative ER and PR, the absence of lymph node metastasis, and high levels of CD8 cells. The overall survival by univariate analysis was positively associated with lower tumor stage, the absence of lymph node metastasis, PD-L1 expression, and high levels of CD8 cells. Therefore, our data suggest cytotoxic immune reaction mediated by CD8-positive T cells and PD-L1 expression may predict a better outcome in patients with HER2-positive breast carcinoma managed with conventional chemotherapy and HER2-blocking therapy. These findings recommend clinical trials utilizing checkpoint blocking immunotherapy in some form for HER2-positive breast cancer.

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“…In particular, PD‐L1 expression has been positively and independently associated with DFS/RFS and/or OS in several unselected primary BC cohorts . In addition, when considering specific BC subtypes, it has been suggested that PD‐L1 protein expression may retain a positive prognostic role in TNBC and in HER2+ BC, in both trastuzumab‐treated and untreated patients .…”

Section: Methodsmentioning

confidence: 99%

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. Implications for Practice In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.

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Expression of Programmed Death Receptor Ligand 1 with High Tumor-Infiltrating Lymphocytes Is Associated with Better Prognosis in Breast Cancer

Cited by 72 publications

References 30 publications

PD-L1 Expression and Tumor-infiltrating Lymphocytes in Breast Cancer: Clinicopathological Analysis in Women Younger than 40 Years Old

PD-L1 Expression and Tumor-infiltrating Lymphocytes in Breast Cancer: Clinicopathological Analysis in Women Younger than 40 Years Old

PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

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