Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

Shinchi, Yusuke; Komohara, Yoshihiro; Yonemitsu, Kimihiro; Sato, Kensaku; Ohnishi, Koji; Saito, Yoichi; Fujiwara, Yukio; Mori, Takeshi; Shiraishi, Kenji; Ikeda, Koei; Suzuki, Makoto

doi:10.1111/cas.14128

Cited by 34 publications

(36 citation statements)

References 26 publications

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“…Yu H et al 33 found that 46.7% and 61.5% of squamous specimens had positive PD‐L1 expression on TCs and ICs. While Shinchi Y et al 34 only detected a positive PD‐L1 expression rate of 26.8% in adenocarcinoma NSCLC. Two retrospective analyses also indicated a higher percentage of PD‐L1 expression in squamous than adenocarcinoma NSCLC (72.3% vs. 36.9% and 34.3% vs. 4.1%, respectively) 35,36 .…”

Section: Immune Escape Mechanisms In Squamous and Adenocarcinoma Nsclcmentioning

confidence: 90%

Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC

et al. 2020

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Immune checkpoint blockades (ICBs) have changed the standard of care of squamous and adenocarcinoma non‐small cell lung cancer (NSCLC). Whereas detailed researches regarding ICBs in the two major histological subtypes are rare. In order to uncover the clinical efficacy differences between squamous and adenocarcinoma NSCLC and better understand the underlying immune‐regulatory mechanisms, we compared the survival benefits of ICBs between the two subtypes by revealing phase 3 randomized trials and attempted to uncover the immune‐regulatory discrepancy. Generally, compared with nonsquamous NSCLC, squamous NSCLC benefited more from ICBs in Keynote 024, CheckMate 026, CheckMate 227 and CheckMate 017 and similar in OAK, but less in Keynote 010 and PACIFIC. We revealed that the tumor mutation burden (TMB) level, the programmed cell death ligand 1 (PD‐L1) expression, tumor infiltrating lymphocytes (TILs) in the tumor microenvironment (TME), chemokines, and oncogenic driver alterations within the two subtypes may contributed to the clinical outcomes of ICBs. We prospected that the combinations of ICBs with chemotherapy, radiation therapy, and antiangiogenic therapy could be promising strategies to re‐immunize the less immunogenic tumors and further enhance the efficacy of ICBs.

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Section: Immune Escape Mechanisms In Squamous and Adenocarcinoma Nsclcmentioning

confidence: 90%

Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC

et al. 2020

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“…However, little is known about the relationship between 18 F-FDG uptake and PD-L1 expression in patients with TETs. Moreover, anti-PD-1 antibody has been already known to provide an optimal blockade of PD-L1 and PD-L2, and some reports have shown that the expression of PD-L2 may be a potential progressive and prognostic marker in lung cancer 13 14 . Nevertheless, it remains unclear whether PD-L2 expression is associated with 18 F-FDG uptake and tumor aggressiveness in patients with about the correlation between PD-L1 expression and metabolic tumor volume (MTV) or total lesion glycolysis (TLG) on 18 F-FDG uptake.…”

Section: Introductionmentioning

confidence: 99%

Tumor Immunity is Related to 18F-FDG Uptake in Thymic Epithelial Tumor

Imai

Kaira

Hashimoto

et al. 2020

Preprint

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Background2-Deoxy-2-[fluorine-18]-fluoro-d-glucose (18F-FDG) positron emission tomography (18F-FDG-PET) is a convenient modality to assess metabolic activity within tumor cells. However, there is no consensus regarding the relationship between 18F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between 18F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs. MethodsA total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and 18F-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1α, VEGFR2, VEGF-C and β2 adrenergic receptor. ResultsHigh uptakes of SUVmax, SUVmean, MTV and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%) and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS of 1-2, thymic carcinoma and advanced stage, and SUVmax on 18F-FDG uptake displayed a close association with PD-L1 and PD-L2 expression, but not MTV and TLG. Multivariate analysis revealed that SUVmax was identified as an independent predictor for positive PD-L1 /PD-L2 expression. GLUT1 was clarified as a significant marker for the expression of PD-L1/PD-L2 from the biological viewpoint. Conclusion18F-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect glucose metabolism and hypoxia in thymic tumor cells.

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“…CD80 can interact with CD28 receptors on T cells, reduce the threshold of T cell activation, and promote the survival of T cells (38,39). Moreover, Shinchi et al (21) found that patients with high expression of PD-L2 (TPS ≥ 1%) had longer OS and PFS in lung adenocarcinoma. In lung squamous cell carcinoma, Matsubara et al ( 22) also pointed out that higher expression of PD-L2 had longer OS than patients with lower expression.…”

Section: Discussionmentioning

confidence: 99%

“…Among renal cell carcinoma patients, the high expression of PD-L2 indicates progression-free survival (PFS) shortening (17). However, some studies hold different views; Shinchi et al (21) and Matsubara et al (22) found that lung cancer patients with high PD-L2 expression had longer DFS and PFS than those with low PD-L2 expression. In hematological tumors, PD-L2 can reflect the degree of immune cell infiltration in follicular lymphoma (FL) and low density of PD-L2 was the most sensitive/specific marker to segregate patients with adverse outcomes (23).…”

Section: Introductionmentioning

confidence: 99%

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Expression and Prognostic Significance of PD-L2 in Diffuse Large B-Cell Lymphoma

Chen

et al. 2021

Front. Oncol.

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Recent studies suggest that programmed death ligand-2 (PD-L2) constitutes an important antitumor immune response. Here, we investigated the relationship between PD-L2 expression and clinicopathological features in diffuse large B-cell lymphoma (DLBCL). Immunohistochemistry showed that positive expression of PD-L2 was observed in 45 of 181 newly diagnosed patients, including 14 cases with expression exclusively on tumor cells (TCs) and 31 cases with the expression on both TCs and immune cells (ICs) in the tumor microenvironment (TME). In 21 recurrent patients, positive expression of PD-L2 was present in six cases, including two cases with expression exclusively on TCs, and four cases with the expression on both TCs and ICs in the TME. Patients with PD-L2 tumor proportion score (TPS) ≥1% exhibited a better ECOG performance status (PS) (ECOG PS score <2, P = 0.041), lower international prognostic index (IPI) score (P < 0.001), and early Ann Arbor stage (Ann Arbor stage I or II, P = 0.010). Similarly, patients with PD-L2 immune proportion score (IPS) ≥1% also exhibited a better ECOG PS (ECOG PS score < 2, P = 0.006) and lower IPI score (P = 0.001). Survival analysis showed that patients with PD-L2 TPS ≥1% exhibited prolonged overall survival (OS) and progression-free survival (PFS). However, survival analysis showed no prognostic significance based on expression of PD-L2 on ICs in the TME. TC PD-L2 expression was significantly associated with OS (P = 0.041) and PFS (P = 0.001). In the multivariate analysis, TC PD-L2 expression was an independent prognostic risk factor for PFS (P = 0.013), but not for OS (P = 0.249). Furthermore, we found that higher TC and IC PD-L2 expression was associated with higher objective response rate (ORR). Moreover, we demonstrated that the expression level of PD-L2 was positively correlated with the expression status of M1 macrophage markers CD86. Our findings highlight PD-L2 as a promising therapeutic target in DLBCL.

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Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

Cited by 34 publications

References 26 publications

Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC

Clinical outcomes of immune checkpoint blockades and the underlying immune escape mechanisms in squamous and adenocarcinoma NSCLC

Tumor Immunity is Related to 18F-FDG Uptake in Thymic Epithelial Tumor

Expression and Prognostic Significance of PD-L2 in Diffuse Large B-Cell Lymphoma

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