Tumor B7-H1 and B7-H3 Expression in Squamous Cell Carcinoma of the Lung

Boland, Jennifer M.; Kwon, Eugene D.; Harrington, Susan M.; Wampfler, Jason A.; Tang, Hui; Yang, Ping; Aubry, Marie Christine

doi:10.1016/j.cllc.2012.05.006

Cited by 171 publications

(141 citation statements)

References 36 publications

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“…Moreover, PD-L1 expression has been associated with poor prognosis and adverse clinicopathological characteristics (28,31,(43)(44)(45)(46). In line with these findings, we have found moderate to high PD-L1 expression in 52.2% to 61.7% of primary prostate cancers after RP.…”

Section: Discussionsupporting

confidence: 78%

The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer

Gevensleben

Dietrich

Golletz

et al. 2016

Clinical Cancer Research

186

189

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Purpose: Therapies targeting the programmed death 1 (PD-1)/ programmed death ligand 1 (PD-L1) pathway promote antitumor immunity and have shown promising results in various tumors. Preliminary data further indicate that immunohistochemically detected PD-L1 may be predictive for anti-PD-1 therapy. So far, no data are available on PD-L1 expression in primary prostate cancer.Experimental Design: Following validation of a monoclonal antibody, immunohistochemical analysis of PD-L1 expression was performed in two independent, well-characterized cohorts of primary prostate cancer patients following radical prostatectomy (RP), and resulting data were correlated to clinicopathological parameters and outcome.Results: In the training cohort (n ¼ 209), 52.2% of cases expressed moderate to high PD-L1 levels, which positively correlated with proliferation (Ki-67, P < 0.001), Gleason score (P ¼ 0.004), and androgen receptor (AR) expression (P < 0.001).Furthermore, PD-L1 positivity was prognostic for biochemical recurrence [BCR; P ¼ 0.004; HR, 2.37; 95% confidence interval (CI), 1.32-4.25]. In the test cohort (n ¼ 611), moderate to high PD-L1 expression was detected in 61.7% and remained prognostic for BCR in univariate Cox analysis (P ¼ 0.011; HR, 1.49; 95% CI, 1.10-2.02). The correlation of Ki-67 and AR with PD-L1 expression was confirmed in the test cohort (P < 0.001).In multivariate Cox analysis of all patients, PD-L1 was corroborated as independently prognostic for BCR (P ¼ 0.007; HR, 1.46; 95% CI, 1.11-1.92).Conclusions: We provide first evidence that expression of the therapy target PD-L1 is not only highly prevalent in primary prostate cancer cells but is also an independent indicator of BCR, suggesting a biologic relevance in primary tumors. Further studies need to ascertain if PD-1/PD-L1-targeted therapy might be a treatment option for hormone-na€ ve prostate cancers.

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Section: Discussionsupporting

confidence: 78%

The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer

Gevensleben

Dietrich

Golletz

et al. 2016

Clinical Cancer Research

186

189

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“…Previous studies revealed controversy in the prognostic value of PD-L1 for NSCLC. There are some studies suggesting a negative prognostic role (17,(21)(22)(23), while others did not find any prognostic value (24,25). However, other studies reported improved patient outcomes (20,26).…”

Section: Resultsmentioning

confidence: 93%

Prognostic significance of programmed cell death ligand 1 (pd-l1), cd8+ tumor-infiltrating lymphocytes and p53 in non-small cell lung cancer: an immunohistochemical study

Rashed

Abdelrahman²,

Abdelgawad³

et al. 2017

TJPATH

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IntRoduCtIonLung cancer ranks the first in the incidence and mortality rates amongst all malignancies worldwide. Non-small cell lung cancer (NSCLC) constitutes 80% -85% of all diagnosed cases and more than 70% of NSCLC are diagnosed as an advanced or late disease (1).Recognition of tumor antigens by t cells leads to activation of anti-tumor immune reaction mainly by cytotoxic CD+8 tumor infiltrating lymphocytes (tiLs), but malignant cells may have many pathways to evade the immunological destruction. PD-1 is a co-stimulatory molecule on t-cells that inhibits t cell activation. PD-1, which is a 288-amino acid cell-surface protein, can bind two ligands, PD-L1 and PD-L2, which negatively control the immune response. tumor cells express PD-L1 can inhibit t cell-mediated immune response and can progress to distant metastasis (2,3). CD8 marker is expressed on cytotoxic t cells, natural killer, and dendritic cells. CD8+ t cells are a major component of the cell-mediated immune system against malignant cells. CD8+ t cells undergo differentiation to effector cytotoxic t cells. Then the effector CD8+ cells undergo apoptosis leaving memory cells when a pathogenic response is resolved. Memory t cells and cytotoxic t cells are associated with a more favorable prognosis in NSCLC (4).PD-L1 over-expression has been proved to be a poor prognostic marker in many human cancers (5). PD-1/ PD-L1 interaction suppresses CD8+ tiLs survival and proliferation and leads to apoptosis of tumor-infiltrating lymphocytes. PD-L1 over-expression in tumor cells in a syngeneic transplant model of tumor cells makes them evade from cytotoxic tiLs (6). AbStRACtObjective: Programmed cell death ligand-1 interacts with the immune receptors on the surface of CD8+ tumor infiltrating lymphocytes and PD-1, thereby blocking its anti-tumor activity. therapeutics suppression of this interaction will show a promise in the treatment of non-small cell lung cancer by restoring the functional anti-tumor t-cell activity. We aimed to evaluate the association between the immunohistochemical expression of PD-L1, stromal CD8+ tumor infiltrating lymphocytes and p53 with the clinicopathological characteristics, response to chemotherapy, progression-free-survival, and overall survival. Material and Method:We examined the immunohistochemical expression of PD-L1, stromal CD8+ tiLs, and p53 expression in 50 patients with advanced stage (iii&iV) non-small cell lung cancer.Results: PD-L1 was expressed in 56% of the studied cases. PD-L1 expression was related to unfavorable response to the therapy without significant difference. PD-L1 expression was significantly associated with disease progression, poor progression-free-survival & overall survival. CD8+ tiLs were high in 32% of the cases. tumors with high CD8+ tiLs showed a partial response to therapy and had a better progression-free-survival and overall survival. p53 expressed in 82% of the studied cases. there was a significant negative association between PD-L1 and CD8+ tiLs (p=0.009), while a non-significant association wa...

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“…26 Another study of squamous NSCLC with the 5H1 antibody observed fewer positive cases (n D 214, PD-L1 TC positive 19.6%). 27 Both studies also detected PD-L1 expression in early and advanced stage NSCLC.…”

Section: Discussionmentioning

confidence: 96%

“…In AD, mutations in KRAS and TP53 and wildtype STK11 were strongly associated with PD-L1 expression, both as individual parameters and as combination in multivariate analysis. Previous studies did not report a correlation of PD-L1 IHC and KRAS status; 26,27 however, these studies only evaluated KRAS exon 2.…”

Section: Pd-l1 Expression (Tumor Cells)mentioning

confidence: 95%

PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations

et al. 2016

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Inhibition of the PD-1/PD-L1 pathway may induce anticancer immune responses in non-small cell lung cancer (NSCLC). Two PD-L1 immunohistochemistry (IHC) assays have been approved as companion diagnostic tests for therapeutic anti-PD-1 antibodies. However, many aspects of PD-L1 prevalence and association with genetically defined subtypes have not been addressed systematically. Here, we analyzed PD-L1 expression in 436 genetically annotated NSCLC specimens enriched for early stages using PD-L1 antibody 5H1. Expression of PD-L1 was detected in the tumor cells (TC) (34% of cases) and in associated immune cells (IC) (49%) across all stages of NSCLC, either alone or in combination. PD-L1 IHC-positive TC, but not IC showed significantly higher PD-L1 RNA expression levels. Expression in TC was associated with TP53, KRAS and STK11 mutational status in adenocarcinomas (AD) and with NFE2L2 mutations in squamous cell carcinomas (SQ). No correlations with histological subtype, clinical characteristics and overall survival were found. The presence of PD-L1-positive IC was significantly associated with patients' smoking status in AD. The findings are in agreement with the emerging concept that tumors with high mutational burden are more likely to benefit from immunotherapy, since TP53 and KRAS mutations are linked to smoking, increased numbers of somatic mutations and expression of neoantigens. Current clinical studies focus on stage IIIB and IV NSCLC; however, PD-L1 expression occurs in earlier stages and might be a predictive biomarker in clinical trials testing (neo-) adjuvant strategies.

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Tumor B7-H1 and B7-H3 Expression in Squamous Cell Carcinoma of the Lung

Cited by 171 publications

References 36 publications

The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer

The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer

Prognostic significance of programmed cell death ligand 1 (pd-l1), cd8+ tumor-infiltrating lymphocytes and p53 in non-small cell lung cancer: an immunohistochemical study

PD-L1 expression in non-small cell lung cancer: Correlations with genetic alterations

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